Publications by authors named "Chuanbao Zhang"

140 Publications

T-Cell Exhaustion Status Under High and Low Levels of Hypoxia-Inducible Factor 1α Expression in Glioma.

Front Pharmacol 2021 9;12:711772. Epub 2021 Jul 9.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Hypoxia-inducible factor 1α (HIF1A), the principal regulator of hypoxia, is involved in the suppression of antitumor immunity. We aimed to describe the T-cell exhaustion status of gliomas under different levels of HIF1A expression. In this study, 692 patients, whose data were collected from the Chinese Glioma Genome Atlas (CGGA) database, and 669 patients, whose data were collected from The Cancer Genome Atlas database, were enrolled. We further screened the data of a cohort of paired primary and recurrent patients from the CGGA dataset (n = 50). The abundance of immune cells was calculated using the transcriptome data. The association between HIF1A and T-cell exhaustion-related genes and immune cells was investigated. According to the median value of HIF1A expression, gliomas were classified into low-HIF1A-expression and high-HIF1A-expression groups. The expression levels of PDL1 (CD274), FOXO1, and PRDM1 in the high-HIF1A-expression group were significantly higher in both glioblastoma (GBM) and lower-grade glioma. The abundance of exhausted T cells and B cells was significantly higher in the high-HIF1A-expression group, while that of macrophage, monocyte, and natural killer cell was significantly higher in the low-HIF1A-expression group in both GBM and lower-grade glioma. After tumor recurrence, the expression of HIF1A significantly increased, and the correlation between HIF1A expression levels and exhausted T cells and induced regulatory T cells became stronger. In diffuse gliomas, the levels of T-cell exhaustion-associated genes and the abundance of immune cells were elevated under high HIF1A expression. Reversing hypoxia may improve the efficacy of immunotherapy.
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http://dx.doi.org/10.3389/fphar.2021.711772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299942PMC
July 2021

Glioma-related epilepsy in patients with diffuse high-grade glioma after the 2016 WHO update: seizure characteristics, risk factors, and clinical outcomes.

J Neurosurg 2021 Jul 9:1-9. Epub 2021 Jul 9.

1Beijing Neurosurgical Institute, Capital Medical University.

Objective: The aim of this study was to investigate the epidemiological characteristics, associated risk factors, and prognostic value of glioma-related epilepsy in patients with diffuse high-grade gliomas (DHGGs) that were diagnosed after the 2016 updated WHO classification was released.

Methods: Data from 449 patients with DHGGs were retrospectively collected. Definitive diagnosis was reaffirmed according to the 2016 WHO classification. Seizure outcome was assessed using the Engel classification at 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors associated with preoperative and postoperative glioma-related epilepsy. Lastly, the prognostic value of glioma-related epilepsy was evaluated by Kaplan-Meier and Cox analysis.

Results: The incidence of glioma-related epilepsy decreased gradually as the malignancy of the tumor increased. Age < 45 years (OR 2.601, p < 0.001), normal neurological function (OR 3.024, p < 0.001), and lower WHO grade (OR 2.028, p = 0.010) were independently associated with preoperative glioma-related epilepsy, while preoperative glioma-related epilepsy (OR 7.554, p < 0.001), temporal lobe involvement (OR 1.954, p = 0.033), non-gross-total resection (OR 2.286, p = 0.012), and lower WHO grade (OR 2.130, p = 0.021) were identified as independent predictors of poor seizure outcome. Furthermore, postoperative glioma-related epilepsy, rather than preoperative glioma-related epilepsy, was demonstrated as an independent prognostic factor for overall survival (OR 0.610, p = 0.010).

Conclusions: The updated WHO classification seems conducive to reveal the distribution of glioma-related epilepsy in DHGG patients. For DHGG patients with high-risk predictors of poor seizure control, timely antiepileptic interventions could be beneficial. Moreover, glioma-related epilepsy (especially postoperative glioma-related epilepsy) is associated with favorable overall survival.
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http://dx.doi.org/10.3171/2020.12.JNS203351DOI Listing
July 2021

New-Onset Postoperative Seizures in Patients With Diffuse Gliomas: A Risk Assessment Analysis.

Front Neurol 2021 18;12:682535. Epub 2021 Jun 18.

Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Glioma-related epilepsy (GRE) is the most common presenting sign of patients with diffuse glioma. According to clinical experience, new-onset postoperative seizures can be observed even in patients without preoperative GRE. The current study mainly aimed to explore the risk factors of new-onset postoperative seizures in those patients. In addition, the prognostic value of new-onset postoperative seizures was also discussed. Data of 313 patients without GRE were retrospectively reviewed. Chi-square test or Fisher's exact test were first performed to compare categorical variables between patients with new-onset postoperative seizures and those without. Subsequently, binary logistic regression analysis was conduct to further assess risk factors of new-onset postoperative seizures. Kaplan-Meier and Cox analysis were used to investigate the prognostic value of new-onset postoperative seizures for progression-free survival (PFS) and overall survival (OS). Patients with low-grade tumors ( = 0.006), isocitrate dehydrogenase 1 (IDH1) mutation ( = 0.040) or low Ki-67 expression ( = 0.005) showed a higher incidence of new-onset postoperative seizures. IDH1 mutation was identified as the only independent predictor for new-onset postoperative seizures (OR, 2.075; 95% CI, 1.051-4.098; = 0.035). Additionally, new-onset postoperative seizure occurrence was demonstrated as an independent predicter of prolonged OS (OR, 0.574; 95% CI, 0.335-0.983; = 0.043), while younger age, gross total resection, low-grade and IDH1 mutation were independently correlated with prolonged OS and PFS. IDH1 mutation is an independent predictor for new-onset postoperative seizures in patients without preoperative GRE. Moreover, new-onset postoperative seizures can independently predict prolonged OS in those patients. The results of the current study can contribute to improving the individualized management of diffuse glioma.
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http://dx.doi.org/10.3389/fneur.2021.682535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250134PMC
June 2021

Comparability of thyroid-stimulating hormone immunoassays using fresh frozen human sera and external quality assessment data.

PLoS One 2021 15;16(6):e0253324. Epub 2021 Jun 15.

Department of Clinical Laboratory, Beijing Chaoyang Hospital, Beijing Center for Clinical Laboratories, The Third Clinical Medical College of Capital Medical University, Beijing, P.R. China.

Background: This study aimed to assess the comparability among assays using freshly frozen human sera and external quality assessment (EQA) data in China.

Methods: Twenty-nine serum samples and two commercial EQA materials, obtained from the National Center for Clinical Laboratories (NCCL), were analyzed in triplicate using eight routine TSH assays. The commutability of commercial EQA materials (NCCL materials) was evaluated in accordance with the CLSI EP30-A and IFCC bias analysis. Median values obtained for the NCCL EQA materials were used to determine the systematic and commutability-related biases among immunoassays through back-calculation. The comparability of TSH measurements from a panel of clinical samples and NCCL EQA data was determined on the basis of Passing-Bablok regression. Furthermore, human serum pools were used to perform commutable EQA.

Results: NCCL EQA materials displayed commutability among three or five of seven assay combinations according CLSI or IFCC approach, respectively. The mean of systematic bias ranged from -13.78% to 9.85% for the eight routine TSH assays. After correcting for systematic bias, averaged commutability-related biases ranged between -42.26% and 12.19%. After correction for systematic and commutability -related biases, the slopes indicating interassay relatedness ranged from 0.801 to 1.299 using individual human sera, from 0.735 to 1.254 using NCCL EQA data, and from 0.729 to 1.115 using pooled human serum EQA(the commutable EQA).

Conclusions: The harmonization of TSH measurement is challenging; hence, systematic and commutability-related biases should be determined and corrected for accurate comparisons among assays when using human individual serum and the commercial EQA materials.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205121PMC
June 2021

Mechanistic Study of the -Quaternized Pyridoxal-Catalyzed Biomimetic Asymmetric Mannich Reaction: Insights into the Origins of Enantioselectivity and Diastereoselectivity.

J Org Chem 2021 05 8;86(9):6592-6599. Epub 2021 Apr 8.

Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.

Density functional theory calculations have been performed to gain insights into the catalytic mechanism of the -quaternized pyridoxal (i.e., )-mediated biomimetic asymmetric Mannich reaction of -butyl glycinate with -diphenylphosphinyl imine to give the diamino acid ester in high yield with excellent enantiomeric and diastereomeric selectivity ( , , 1438). The study reveals that the whole catalysis can be characterized via three stages: (i) the catalyst reacts with the -butyl glycinate to generate the active carbanion complex . (ii) then reacts with the -diphenylphosphinyl imine giving the imine intermediate . (iii) undergoes hydrolysis to give the final product anti- and regenerate the catalyst for the next catalytic cycle. Each stage is kinetically and thermodynamically feasible for experimental realization. The hydrolysis step in the stage III is predicted to be the rate-determining step during the whole catalytic cycle. Furthermore, the origins of the enantioselectivity and diastereoselectivity for the target reaction, as well as the deactivation of the catalyst , are also discussed.
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http://dx.doi.org/10.1021/acs.joc.1c00381DOI Listing
May 2021

MicroRNA-935 Directly Targets FZD6 to Inhibit the Proliferation of Human Glioblastoma and Correlate to Glioma Malignancy and Prognosis.

Front Oncol 2021 12;11:566492. Epub 2021 Mar 12.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

MicroRNAs (miRNAs) are involved in human glioblastoma (GB). MiR-935 has been reported to have both tumor-inhibiting and tumorigenesis effects, but its role in GB remains unclear. Because of the high mortality and morbidity associated with the malignancy of GB, a deeper understanding of the molecular crosstalk that occurs in GB is needed to identify new potential targets for treatment. At present, the mechanism of GB at the molecular level is not fully understood. With the aid of bioinformatic analysis, miR-935 was significantly downregulated in GB, and it presented a poorer outcome. In the glioma cell line and in the nude mice model, the miR-935 inhibited cell proliferation by modulating cell circles and . Then, the target genes of miR-935 were analyzed by using the online database, and the direct binding was tested with a luciferase analysis. FZD6 was found to be the direct target of miR-935. The effect of miR-935 was recovered by the overexpression of FZD6 . In addition, the negative correlation of miR-935 and the expression of FZD6 were confirmed in our clinical samples, and the expression of FZD6 has a strong correlation with tumor malignancy and prognosis. This study showed that miR-935 directly inhibited the expression of FZD6 and inhibited the cell proliferation, thereby suppressing the development of GB, suggesting that miR-935 is a cancer suppressor miRNA and may become a prognostic biomarker or a promising potential therapeutic target for human GBs.
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http://dx.doi.org/10.3389/fonc.2021.566492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006443PMC
March 2021

Development of a designated comparison method for alkaline phosphatase measurements and its application to evaluating routine methods.

Scand J Clin Lab Invest 2021 May 23;81(3):218-224. Epub 2021 Mar 23.

Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing, China.

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) published the reference measurement procedure (RMP) for ALP measurement in 2011. However, the RMP is of high requirements for laboratories, complicated, time-consuming and high cost of reagents. Many manufacturers do not trace results to the higher procedure. And there is currently no designated comparison method (DCM) for ALP measurement. Thus, the standardization of ALP measurement is hindered. Automatic biochemical analyzers are easy to operate and widely used in clinical laboratories. Therefore, according to the RMP, establishing a DCM based on an automatic biochemical analyzer will be a practical way to establish traceability to the accuracy base and promote the standardization of ALP measurement. On the basis of conforming to the RMP recommended by IFCC as far as possible, the DCM was established based on a Thermo Indiko automatic biochemical analyzer. Performances of the method were validated. The DCM repeatability and within laboratory imprecision was <1% and <2.5%, respectively. For evaluation of trueness, the biases were within the equivalent limits. Measurement procedure comparisons and biases estimation were carried out between the DCM, the RMP, and the six routine methods using a panel of 40 individual human serum samples. The comparisons between the DCM and the RMP gave satisfying results. Compared with the DCM, the relative biases of some routine methods failed to meet the bias limit derived from biological variation.
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http://dx.doi.org/10.1080/00365513.2021.1901305DOI Listing
May 2021

Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients.

Genomics Proteomics Bioinformatics 2021 Mar 2. Epub 2021 Mar 2.

Beijing Neurosurgical Institute, Capital Medical University, Beijing 100070, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China; Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing 100069, China; China National Clinical Research Center for Neurological Diseases, Beijing 100070, China. Electronic address:

Gliomas are the most common and malignant intracranial tumors in adults. Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments. However, access to comprehensive genomic data and analytical platforms is often limited. Here, we developed the Chinese Glioma Genome Atlas (CGGA), a user-friendly data portal for the storage and interactive exploration of cross-omics data, including nearly 2000 primary and recurrent glioma samples from Chinese cohort. Currently, open access is provided to whole-exome sequencing data (286 samples), mRNA sequencing (1018 samples) and microarray data (301 samples), DNA methylation microarray data (159 samples), and microRNA microarray data (198 samples), and to detailed clinical information (age, gender, chemoradiotherapy status, WHO grade, histological type, critical molecular pathological information, and survival data). In addition, we have developed several tools for users to analyze the mutation profiles, mRNA/microRNA expression, and DNA methylation profiles, and to perform survival and gene correlation analyses of specific glioma subtypes. This database removes the barriers for researchers, providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications. CGGA is available at http://www.cgga.org.cn.
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http://dx.doi.org/10.1016/j.gpb.2020.10.005DOI Listing
March 2021

High-sensitive clinical diagnostic method for PTPRZ1-MET and the characteristic protein structure contributing to ligand-independent MET activation.

CNS Neurosci Ther 2021 May 28;27(5):617-628. Epub 2021 Feb 28.

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Background: PTPRZ1-MET (ZM) is a critical genetic alteration driving the progression of lower-grade glioma. Glioma patients harboring ZM could benefit from MET inhibitors. According to the remarkable role of ZM as a driver of glioma progression and indicator of MET inhibitor sensitivity, it is necessary to detect this alteration even when it presents in glioma with relatively fewer copies.

Methods: Herein, we proposed that ZM could be detected with a high-sensitive method of reverse transcriptase PCR with 50 amplification cycles. Via this newly proposed detection method, we depicted the incidence preference of ZM fusion in a cohort of 485 glioma patients. To further explore the oncogenic nature of ZM, we predicated the protein structure alteration of MET kinase brought by its fusion partner.

Results: The incidence of ZM fusions was much higher than previous report. ZM fusions exhibited a striking preference in lower-grade glioma and secondary glioblastoma. By contrast, none of patients with primary glioblastoma was detected harboring ZM fusion. In each of the four variants of ZM, the fusion partner segment of MET contained a remarkable coiled-coil motif. In glioma cells expressing ZM, MET kinase could be activated in a ligand-independent manner, which might be contributed by the special coiled-coil structure brought by the fusion partner. Corresponding to the 3D structural analysis and cell line experiment, the ZM positive clinical specimens showed hyperactivations of MET signaling.

Conclusions: ZM fusions are critical drivers of glioma progression and effective target of MET inhibitor. Early detection could be performed with a high-sensitive method of reverse transcriptase PCR. The hyperactivations of MET signaling driving glioma progression might be contributed by a ligand-independent activation enabled by the protein structure modification of extracellular domain of MET in ZM fusions.
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http://dx.doi.org/10.1111/cns.13627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025647PMC
May 2021

Achieving the Super Gas-Wetting Alteration by Functionalized Nano-Silica for Improving Fluid Flowing Capacity in Gas Condensate Reservoirs.

ACS Appl Mater Interfaces 2021 Mar 26;13(9):10996-11006. Epub 2021 Feb 26.

College of Petroleum Engineering, China University of Petroleum (East China), Qingdao 266580, China.

It is well-known that the production of gas-condensate reservoirs is significantly affected by the liquid condensation near the wellbore region. Gas-wetting alteration can be one of the most effective approaches to alleviate condensate accumulation and improve liquid distribution. However, gas well deliverability is still limited because the wettability of cores is altered only from liquid-wetting to intermediate gas-wetting by using traditional chemical stimulation. To solve this bottleneck problem, herein, we developed a fluorine-functionalized nanosilica to achieve super gas-wetting alteration, increasing the contact angles of water and n-hexadecane on the treated core surface from 23 and 0° to 157 and 145°, respectively. The surface free energy reduces rapidly from 67.97 to 0.23 mN/m. The super gas-wetting adsorption layer on the core surface formed by functionalized nanosilica not only increases the surface roughness but also reduces the surface free energy. The core flooding confirms that the required pressure for displacement is apparently reduced. Meanwhile, the core permeability can be dramatically restored after the super gas-wetting alteration. The microscopic visualization is employed to further understand the impact of fluorine-functionalized nanosilica on the fluid flow behavior and mechanism in porous media. The oil saturation in the micromodel decreases sharply from 48.75 to 7.84%, eliminating the "water locking effect" and "Jiamin effect", which indicates that the added functional nanosilica effectively improves fluid flow capacity and may contribute to production in the gas condensate reservoirs. In addition, this work reveals the fluid flow behavior and mechanism in the reservoir in detail, which will expand the better application of this material to many oilfields and other mining engineering systems.
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http://dx.doi.org/10.1021/acsami.0c22831DOI Listing
March 2021

Preparation, stability and commutability of candidate reference materials for lactate dehydrogenase (LDH).

Clin Biochem 2021 May 20;91:45-51. Epub 2021 Feb 20.

The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing 100730, PR China; Clinical Biobank, Beijing Hospital, National Center of Gerontology, Beijing 100730, PR China. Electronic address:

Background: Lactate dehydrogenase (LDH) is a key enzyme that functions as a marker of cell damage. Its activity can be measured by a variety of laboratory methods. To eliminate inter-method bias and enhance equivalence among different measurement procedures, LDH detection needs to be standardized.

Methods: Optimized sequences coding for lactate dehydrogenase subunit A (LDH-A) and subunit B (LDH-B) were synthesized and cloned into the pRSFDuet vector, and then the constructed 6His-LDHA-pRSFDuet, 6His-LDHB-pRSFDuet, and 6His-LDHA-LDHB-pRSFDuet plasmids were transformed into Escherichia coli BL21 (DE3) for expression. The enzyme activity and specific activity of recombinant LDHs were detected. Electrophoresis of LDH isoenzymes was performed. The stability of recombinant LDHs and serum LDH was evaluated. Commutability of recombinant LDH-B was studied by the IFCC reference method and six routine methods.

Results: Three plasmids were constructed and three highly concentrated recombinant LDH isoenzymes were obtained. The specific activities of LDH-A, LDH-AB, and LDH-B were 18.08 U/mg, 21.74 U/mg, and 14.18 U/mg, respectively. There was a desirable linear correlation between the activities of recombinant LDH isoenzymes and their protein concentrations. Electrophoresis of LDH isoenzymes showed that the recombinant LDH-B corresponded to LDH1 and it demonstrated good stability at 4 °C and 25 °C for 5 weeks. LDH-B formulations in saline-bovine serum albumin solution and human serum matrix were commutable for six routine methods.

Conclusion: Human recombinant LDH-B has great potential to become an improved and less expensive standard or reference material in external quality assessment for clinical LDH measurement.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.02.002DOI Listing
May 2021

Identification of a Glycolysis-Related LncRNA Signature to Predict Survival in Diffuse Glioma Patients.

Front Oncol 2020 5;10:597877. Epub 2021 Feb 5.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Glycolysis refers to one of the critical phenotypes of tumor cells, regulating tumor cell phenotypes and generating sufficient energy for glioma cells. A range of noticeable genes [such as isocitrate dehydrogenase (IDH), phosphatase, and tensin homolog (PTEN), or Ras] overall impact cell proliferation, invasion, cell cycle, and metastasis through glycolysis. Moreover, long non-coding RNAs (LncRNAs) are increasingly critical to disease progression. Accordingly, this study aimed to identify whether glycolysis-related LncRNAs have potential prognostic value for glioma patients. First, co-expression network between glycolysis-related protein-coding RNAs and LncRNAs was established according to Pearson correlation (Filter: |r| > 0.5 & P < 0.001). Furthermore, based on univariate Cox regression, the Least Absolute Shrinkage and Selection Operator (LASSO) analysis and multivariate Cox regression, a predictive model were built; vital glycolysis-related LncRNAs were identified; the risk score of every single patient was calculated. Moreover, receiver operating characteristic (ROC) curve analysis, gene set enrichment analysis (GSEA), GO and KEGG enrichment analysis were performed to assess the effect of risk score among glioma patients. 685 cases (including RNA sequences and clinical information) from two different cohorts of the Chinese Glioma Genome Atlas (CGGA) database were acquired. Based on the mentioned methods, the risk score calculation formula was yielded as follows: Risk score = (0.19 × EXP) + (-0.27 × EXP) + (-0.16 × EXP) + (-0.05 × EXP) + (0.11 × EXP) + (0.35 × EXP). The risk score was independently related to prognosis, and every single mentioned LncRNAs was significantly related to the overall survival of patients. Moreover, functional enrichment analysis indicated that the biologic process of the high-risk score was mainly involved in the cell cycle and DNA replication signaling pathway. This study confirmed that glycolysis-related LncRNAs significantly impact poor prognosis and short overall survival and may act as therapeutic targets in the future.
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http://dx.doi.org/10.3389/fonc.2020.597877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892596PMC
February 2021

Novel roles of VAT1 expression in the immunosuppressive action of diffuse gliomas.

Cancer Immunol Immunother 2021 Feb 12. Epub 2021 Feb 12.

Department of Radiotherapy, Fengtai District, Beijing Tiantan Hospital, Capital Medical University, 119 South 4th Ring Road West, Beijing, 100070, China.

Standard treatment regimen of gliomas has almost reached a bottleneck in terms of survival benefit. Immunotherapy has been explored and applied in glioma treatment. Immunosuppression, as a hallmark of glioma, could be alleviated by inhibiting certain abnormally expressed biomarkers. Here, transcriptome data of 325 whole grade gliomas were collected from the CGGA database. The TCGA RNA sequencing database was used for validation. Western blot was used to verify the expression level of VAT1 on cellular level. The results showed that the expression of VAT1 was positively correlated with the grades of glioma as classified by WHO. A higher expression level of VAT1 was observed in the mesenchymal subtype of gliomas. The area under the curve suggested that the expression level of VAT1 might be a potential prognostic marker of mesenchymal subtype. In survival analysis, we found that patients with high VAT1 expression level tended to have shorter overall survival, which indicated the prognostic value of VAT1 expression. The results of gene ontology analysis showed that most biological processes of VAT1-related genes were involved in immune and inflammatory responses. The results of GSEA analysis showed a negative correlation between VAT1 expression and immune cells. We also identified that the expression of immune checkpoints increased with VAT1 expression. Therefore, the high expression level of VAT1 in patients with glioma was a potential indicator of a lower survival rate for patients with gliomas. Remarkably, VAT1 contributed to glioma-induced immunosuppression and might be a novel target in glioma immunotherapy.
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http://dx.doi.org/10.1007/s00262-021-02865-zDOI Listing
February 2021

Targeted exome sequencing for the identification of common mutational signatures and potential driver mutations for brain metastases and prognosis.

Oncol Lett 2021 Mar 6;21(3):179. Epub 2021 Jan 6.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.

Brain metastases (BMs) are malignancies in the central nervous system with poor prognosis. Genetic landscapes of the primary tumor sites have been extensively profiled; however, mutations associated with BMs are poorly understood. In the present study, target exome sequencing of 560 cancer-associated genes in samples from 52 patients with brain metastasis from various primary sites was performed. Recurrent mutations for BMs from distinct origins were identified. There were both genetic homogeneity and heterogeneity between BMs and primary lung tumor tissues. The mutation rate of the major cancer driver gene, , was consistently high in both the primary lung cancer sites and BMs, while some genetic alterations, associated with DNA damage response deficiency, were specifically enriched in BMs. The mutational signatures enriched in BMs could serve as actionable targets for treatment. The mutation in the primary site of the potential brain metastasis driver gene, nuclear mitotic apparatus protein 1 (), affected the progression-free survival time of patients with lung cancer, and patients with the mutation in BMs had a good prognosis. This suggested that the occurrence and clinical outcome of brain metastases could be independent of each other.
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http://dx.doi.org/10.3892/ol.2021.12440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816386PMC
March 2021

Measurement of serum 17-hydroxyprogesterone using isotope dilution liquid chromatography-tandem mass spectrometry candidate reference method and evaluation of the performance for three routine methods.

Clin Chem Lab Med 2021 Feb 25;59(3):523-532. Epub 2020 Nov 25.

National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.

Objectives: Accurate measurements of serum 17-hydroxyprogesterone (17OHP) are essential for diagnosis and treatment monitoring for congenital adrenal hyperplasia patients. The performance of serum 17OHP routine methods remains highly variable that calls for a candidate reference measurement procedure (cRMP) to improve the standardization of serum 17OHP measurements.

Methods: Serum samples spiked with internal standards were extracted with a combination of solid-phase extraction and liquid-liquid extraction. The 17OHP was quantified by the isotope dilution coupled with liquid chromatography/tandem mass spectrometry (ID-LC/MS/MS) with electrospray ionization in positive ion mode. Nine structural analogs of 17OHP were evaluated for interferences. The precision and analytical recovery were assessed. Twenty native and 40 spiked serum for performance evaluation were measured by the cRMP and two clinical LC/MS routine methods.

Results: No apparent interferences were found with the 17OHP measurement. The within-run, between-run, and total precision for our method were 0.4-0.8%, 0.6-2.0%, and 1.0-2.1% for four pooled serum (2.46-102.72 nmol/L), respectively. The recoveries of added 17OHP were 100.0-100.2%. For the performance of two LC/MS routine methods, they showed relative deviation ranges of -22.1 to 1.1% and -6.7 to 12.8%, respectively.

Conclusions: We developed and validated a reliable serum 17OHP method using ID-LC/MS/MS. The desirable accuracy and precision of this method enable it to serve as a promising cRMP to improve the standardization for serum 17OHP routine measurements.
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http://dx.doi.org/10.1515/cclm-2020-0410DOI Listing
February 2021

Commutability of possible external quality assessment materials for progesterone measurement.

Clin Biochem 2021 Jan 12;87:39-45. Epub 2020 Nov 12.

National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, PR China; Chinese Academy of Medical Sciences and Peking Union Medical College, PR China. Electronic address:

Background: The commutability of control materials used for external quality assessment (EQA) programs is of great importance. Evaluating the commutability of control materials is crucial to assess their suitability for EQA programs.

Methods: Forty-eight individual patient serum samples, commercial EQA samples, human serum pools (HSPs), commercially available sterile filtered charcoal stripped serum (CS) and swine serum were analyzed using the isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) comparative method and six immunoassays for progesterone. The commutability was assessed according to the EP14-A2 guideline and the difference in bias approach, respectively.

Results: According to the EP14-A2 guideline, HSPs and CS were commutable for all the tested immunoassays, while swine serum showed positive matrix effects in some assays. Based on the difference in bias approach, a large number of inconclusive and noncommutable results appeared.

Conclusions: The commutability of the processed materials varied depending on which evaluation approach and criterion was applied. Noncommutability of the EQA materials was observed. And HSPs and CS were possible commutable candidate control materials according to the EP14-A2 guideline.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.10.012DOI Listing
January 2021

Clinical practice guidelines for the management of adult diffuse gliomas.

Cancer Lett 2021 02 6;499:60-72. Epub 2020 Nov 6.

Department of Neurosurgery, The Fourth Medical Center of PLA General Hospital, Beijing, 100048, China.

To follow the revision of the fourth edition of WHO classification and the recent progress on the management of diffuse gliomas, the joint guideline committee of Chinese Glioma Cooperative Group (CGCG), Society for Neuro-Oncology of China (SNO-China) and Chinese Brain Cancer Association (CBCA) updated the clinical practice guideline. It provides recommendations for diagnostic and management decisions, and for limiting unnecessary treatments and cost. The recommendations focus on molecular and pathological diagnostics, and the main treatment modalities of surgery, radiotherapy, and chemotherapy. In this guideline, we also integrated the results of some clinical trials of immune therapies and target therapies, which we think are ongoing future directions. The guideline should serve as an application for all professionals involved in the management of patients with adult diffuse glioma and also a source of knowledge for insurance companies and other institutions involved in the cost regulation of cancer care in China and other countries.
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http://dx.doi.org/10.1016/j.canlet.2020.10.050DOI Listing
February 2021

Alpha-fetoprotein accelerates the progression of hepatocellular carcinoma by promoting Bcl-2 gene expression through an RA-RAR signalling pathway.

J Cell Mol Med 2020 12 22;24(23):13804-13812. Epub 2020 Oct 22.

National Center for Clinical Laboratories, National Center of Gerontology, Beijing Hospital, Beijing, China.

Previous studies have found that alpha-fetoprotein (AFP) can promote the proliferation of hepatoma cells and accelerate the progression of hepatocellular carcinoma (HCC). However, the exact mechanism of action remains unclear. Recent bioinformatics studies have predicted the possible interaction between AFP and retinoic acid receptors (RARs). Thus, the purpose of this study was to investigate the molecular mechanism through which AFP promotes tumour cell proliferation by interfering with the RA-RAR signal pathway. Our data indicated that AFP could significantly promote the proliferation and weaken ATRA-induced apoptosis of hepatoma cells. Besides, cytoplasmic AFP interacts with RAR, disrupting its entrance into the nucleus, which in turn affects the expression of the Bcl-2 gene. In addition, knockdown of AFP in HepG2 cells was synchronously associated with an incremental increase of RAR binding to DNA, as well as down-regulation of Bcl-2; the opposite effect was observed in AFP gene-transfected HLE cells. Moreover, a similar effect of AFP was detected in tumour tissues with high serum AFP, but not in adjacent non-cancerous liver tissues, or HCC tissues with low serum AFP levels. These results indicate that AFP acts as signalling molecule and prevents RAR from entering into the nucleus by interacting with RAR, thereby promoting the expression of Bcl-2. Our data reveal a novel mechanism through which AFP regulates Bcl-2 expression and further suggest that AFP may be used as a novel target for treating HCC.
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http://dx.doi.org/10.1111/jcmm.15962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753843PMC
December 2020

Comprehensive analysis of the immunological landscape of pituitary adenomas: implications of immunotherapy for pituitary adenomas.

J Neurooncol 2020 Sep 9;149(3):473-487. Epub 2020 Oct 9.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Purposes: Immunotherapies for solid tumor are gaining traction in the clinic, however, the immunological landscape of pituitary adenomas (PAs) is not well defined. In the present study, we used the RNA-seq data of PAs to investigate the impact of immunological landscape on clinical features of pituitary adenomas and aim to evaluate the potential immunotherapy for PAs.

Methods: We analyzed tumor-infiltrating immune cells in 115 PA samples using RNA-seq. Main immune cell types (B cells, CD8 T cells, CD4 T cells, macrophages and NK cells) were detected from the expression of genes. The association between immune cells abundance and immune checkpoint, as well as inflammatory factors were analyzed. 10 additional patients were enrolled for validation.

Results: In RNA sequencing data, landscape of PAs were identified. Our computationally inferred immune infiltrates significantly associate with patient clinical features. Growth hormone-secreting adenomas (GHomas) were found with higher B cells and CD8 T cells infiltration. Moreover, GHomas showed relative different genetic background, significant invasive behavior and independently correlated with reduced progress-free time. Tumor progression was related to increased expression of PD-1/PD-L1 and was associated with higher immune infiltration. Analysis of cancer-testis antigen expression and CD8 T-cell abundance suggested CTAG2 and TSPYL6 were potential immunotherapeutic targets in GHomas and non-functioning adenomas, respectively.

Conclusions: Tumor-infiltrating immune cells confer important clinical and biological implications. Our results of immune-infiltrate levels in PAs may inform effective cancer vaccine and checkpoint blockade therapies and make it possible to take immunotherapy into invasive PAs.
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http://dx.doi.org/10.1007/s11060-020-03636-zDOI Listing
September 2020

Long-term efficacy of surgical resection with or without adjuvant therapy for treatment of secondary glioblastoma in adults.

Neurooncol Adv 2020 Jan-Dec;2(1):vdaa098. Epub 2020 Aug 21.

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Background: There are limited studies on treatment strategies and associated clinical outcomes in patients with secondary glioblastoma (sGBM). We sought to investigate the prognostic factors and treatment decisions in a retrospective cohort of patients with sGBM.

Methods: One hundred and seventy-one patients with sGBM who met the screening criteria were included in this study. Kaplan-Meier survival analysis and Cox survival analysis were used to detect prognostic factors. R (v3.5.0) and SPSS software (v25.0, IBM) were used to perform statistical analyses.

Results: The median overall survival was 303 days (range 23-2237 days) and the median progression-free survival was 229 days (range 33-1964 days) in patients with sGBM. When assessing the relationship between adjuvant treatment outcome and extent of resection (EOR), the results showed that patients underwent gross total resection can benefit from postoperative radiotherapy and chemotherapy, but not in patients underwent subtotal resection. In addition, we also found that aggressive adjuvant therapy can significantly improve clinical outcomes of IDH1-mutated patients but no significant prognostic value for IDH1-wildtyped patients. The univariate Cox regression analyses demonstrated that EOR, adjuvant therapy, and postoperative Karnofsky Performance Scores were prognostic factors for patients with sGBM, and multivariate COX analysis confirmed that adjuvant therapy and EOR were independent prognostic factors.

Conclusions: For patients with sGBM, aggressive postoperative adjuvant therapy after gross total resection was recommended. However, we did not detect a benefit in IDH1-wildtype patients in our cohort.
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http://dx.doi.org/10.1093/noajnl/vdaa098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513886PMC
August 2020

Identification of PIEZO1 as a potential prognostic marker in gliomas.

Sci Rep 2020 09 30;10(1):16121. Epub 2020 Sep 30.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

In multiple solid tumours, including gliomas, the mechanical properties change as the disease progresses. If and how mechanical cues regulate tumour cell proliferation is currently not fully studied. PIEZO1 has recently been identified as a crucial mechanosensitive cation channel in multiple solid tumours. However, we didn't find any clinical data describing the association between PIEZO1 expression and glioma. To investigate the role of PIEZO1 in gliomas, we analysed PIEZO1 gene expression at the transcriptome level, genomic profiles and the association of PIEZO1 with clinical practice. In total, 1633 glioma samples with transcriptome data, including data from the Chinese Glioma Genome Atlas RNAseq, the Cancer Genome Atlas RNAseq and GSE16011 databases, were included in this study. Clinical information and genomic profiles including somatic mutations were also obtained. We found that PIEZO1 expression was highly correlated with malignant clinical and molecular subtypes of glioma. Gene ontology analysis showed that expression of PIEZO1 was correlated with tumour microenvironment-related genes that encode proteins involved in extracellular matrix (ECM) organization, angiogenesis and cell migration. Additionally, PIEZO1 was shown to be involved in tumour progression by serving as the central checkpoint of multiple ECM remodelling-related signalling pathways to modulate tumour cell proliferation and the tumour microenvironment in turn. Finally, high PIEZO1 expression was correlated with reduced survival time and acted as a robust biomarker for poor prognosis in gliomas. Taken together, the results indicated that high PIEZO1 expression is closely associated with highly malignant gliomas. Importantly, PIEZO1 serves as a key factor involved in sensing mechanical properties in the tumour and can regulate both tumour cells and their microenvironment to promote glioma progression, and it is also a potential therapeutic target for the treatment of gliomas.
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http://dx.doi.org/10.1038/s41598-020-72886-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528027PMC
September 2020

Commutability Assessment of Candidate External Quality Assessment Materials for Aminotransferase Activity Measurements Based on Different Approaches in China.

Ann Lab Med 2021 01 25;41(1):68-76. Epub 2020 Aug 25.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing Engineering Research Center of Laboratory Medicine, Beijing, P. R. China.

Background: Using commutable external quality assessment (EQA) materials is important for monitoring successful harmonization efforts. We assessed the commutability of four human serum pool (HSP) preparations to identify candidate EQA materials for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity measurement.

Methods: One set each of 85 clinical samples (CSs) was collected for ALT and AST activity measurement. The 15 candidate EQA materials included four types of HSP preparations (A to D): materials A, C, and D contained human original recombinant (HOR) aminotransferases; materials B was mixed leftover samples. The CSs and 15 candidate EQA materials were analyzed using seven routine assays, and the ln-transformed results were analyzed in 21 assay pairs. Commutability was assessed using Deming regression, with a 95% prediction interval (CLSI approach) and the difference in bias with an error component model (International Federation of Clinical Chemistry and Laboratory Medicine [IFCC] approach).

Results: For ALT, all materials were commutable for 14-21 assay pairs according to the CLSI and IFCC approaches. For AST, B01-03 showed commutability for 14-21 assay pairs, and C01-03 and D01-03 showed commutability for no less than 10 assay pairs according to the two approaches. A01-06 were commutable for 9-16 assay pairs according to the CLSI approach, but for 6-9 assay pairs according to the IFCC approach.

Conclusions: Mixed leftover samples showed desirable commutability characteristics as candidate EQA materials for routine aminotransferase activity measurements. Human serum bases supplemented with HOR were commutable for most routine ALT activity measurements.
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http://dx.doi.org/10.3343/alm.2021.41.1.68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443529PMC
January 2021

Evaluation of serum electrolytes measurement through the 6-year trueness verification program in China.

Clin Chem Lab Med 2020 07 28;59(1):107-116. Epub 2020 Jul 28.

National Center for Clinical Laboratories, Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, National, Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R. China.

Objectives: The National Center for Clinical Laboratories (NCCL) in China initiated a serum electrolyte trueness verification (ETV) program in 2014 for measurement standardization.

Methods: Every year, two levels of fresh frozen commutable serum samples determined by inductively coupled plasma mass spectrometry (ICP-MS) reference methods were transported to participating clinical laboratories for the measurement of sodium, potassium, calcium and magnesium. Both samples were measured 15 times in 3 days, and the mean values and coefficient variations (CVs) were calculated from the results. The tolerance limits of trueness (bias), precision (CV) and accuracy (TE) based on the biological variation database were used as the evaluation criteria. The overall trend of the ETV program over 6 years was surveyed by calculating the pass rates of the participating laboratories. The mean bias, inter-laboratory CV, and TE of all laboratory results were analysed. Furthermore, homogeneous and heterogeneous systems were compared, and the bias and CV results of mainstream analysis systems were analysed.

Results: Pass rates of the three quality specifications increased, and the overall mean bias and inter-laboratory CVs decreased. The homogeneous system was superior to the heterogeneous system for calcium and magnesium measurements. For sodium, potassium, calcium and magnesium, the minimum bias corresponded to Hitachi, Siemens, Beckman AU and Roche, respectively. For inter-laboratory robust CVs, no obvious differences were observed between each peer group.

Conclusions: The commutable ETV materials assigned via reference methods can evaluate the accuracy and reproducibility of an individual laboratory and the calibration traceability and uniformity between laboratories for measurements.
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http://dx.doi.org/10.1515/cclm-2020-0355DOI Listing
July 2020

Effects of calcium dobesilate (CaD) interference on serum creatinine measurements: a national External Quality Assessment (EQA)-based educational survey of drug-laboratory test interactions.

Clin Chem Lab Med 2020 07 12;59(1):139-145. Epub 2020 Jul 12.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, PR China.

Objectives: Drug-laboratory test interactions (DLTIs) are one of the major sources of laboratory errors. Calcium dobesilate (CaD) interference on serum creatinine testing is a widespread problem that has long been ignored in China. A national EQA-based survey was launched to investigate the current status of CaD interference on creatinine routine methods used in China and enhance the education of CaD interference in clinical laboratories.

Methods: A descriptive survey was developed to characterize the status quo of Chinese laboratory professionals' cognition to CaD interference. Four of survey samples which were spiked with/without interference additive were shipped to 175 participant laboratories. The target reference values from a reference measurement procedure were compared against the results from participating laboratories to evaluate the CaD interference on serum creatinine measurements using enzymatic method or Jaffé method.

Results: The lack of knowledge of DLTIs and the barriers to collect information from pharmacological and laboratory data systems had become the main problems on implementing DLTIs education in China. A significant negative influence of CaD on enzymatic method was observed regardless of measurement platforms. Jaffé method was generally free from interaction with CaD but showed poor precision and accuracy at low creatinine concentrations.

Conclusions: More efforts should be made to enhance the education of DLTIs in clinical laboratories in China.
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http://dx.doi.org/10.1515/cclm-2020-0424DOI Listing
July 2020

Prognostic value of a nine-gene signature in glioma patients based on tumor-associated macrophages expression profiling.

Clin Immunol 2020 07 20;216:108430. Epub 2020 Apr 20.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, China; Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, China. Electronic address:

Tumor-associated macrophages (TAMs) are regarded as the most abundantly infiltrating immune cells around the tumor microenvironment in gliomas, which plays an important role in tumorgenesis and immunosuppression. A total of 216 patients diagnosed with primary glioma were obtained from the Chinese Glioma Genome Atlas of which the RNA sequencing data was used as training set. RNA sequencing from the Cancer Genome Atlas was applicated for validation. We found that mesenchymal subtype showed strong positive correlation with macrophage-related genes (MRGs) expression. Survival analysis showed that high expression level of MRG predicted poor prognosis. A TAM-based nine-gene signature was constructed, which divided the samples into high- and low-risk of unfavorable outcome. The result of Cox regression analysis showed that the risk score was an independent prognostic factor in gliomas. Hence, the expression of TAMs was correlated with patient survival. The nine-TAM-related gene signature can predict patient survival efficiently.
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http://dx.doi.org/10.1016/j.clim.2020.108430DOI Listing
July 2020

Commutability of reference materials for alkaline phosphatase measurements.

Scand J Clin Lab Invest 2020 Sep 9;80(5):388-394. Epub 2020 Apr 9.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, People's Republic of China.

Commutability is a prerequisite when using a candidate reference materials (CanRMs) for calibration and trueness control of routine methods or for value transfer from the reference method to end-user calibrators of routine methods through a calibration hierarchy. The CanRMs include commercial general chemistry materials (GCs), enzyme trueness verification materials (ETVs), and secondary reference materials (SRMs). The commutability of CanRMs was evaluated based on the difference in bias and EP14-A3 to investigate their suitability for ALP measurement. A total of 44 fresh individual clinical samples (CSs) and the CanRMs were analyzed by six routine methods (validated methods) and by IFCC primary reference method (comparative method) for the determination of Alkaline Phosphatase (ALP). The commutability was performed based on IFCC working group recommendations for assessing commutability and analyzed according to EP14-A3 guide and difference in bias approach, respectively. The bias of the routine methods was assessed according to CLSI guidelines. The result of commutable materials obtained from the two evaluation approaches are not significantly different. It was observed that the routine methods with lower bias were associated with more commutable CanRMs. None of the CanRMs were suitable for use as commutable RMs. The findings of this study have a number of important implications for future practice.
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http://dx.doi.org/10.1080/00365513.2020.1747111DOI Listing
September 2020

Hemangiopericytomas: Spatial Intracranial Location in a Voxel-Based Mapping Study.

J Neuroimaging 2020 05 1;30(3):370-377. Epub 2020 Apr 1.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.

Background And Purpose: To investigate the preferred location of intracranial hemangiopericytomas (IHPCs) with voxel-based mapping and 3-dimensional reconstruction from MRI data.

Methods: Gadolinium-enhanced tumors of 258 primary and single IHPCs were segmented semi-automatically, followed by manual checking and editing of boundaries. The lesions were registered to Montreal Neurological Institute standard anatomical space, and heat-map and 3-dimensional rendered frequency images were generated. All tumors were then superimposed on the Anatomical Automatic Labeling (AAL) template to further investigate the difference in the tumor location based on the voxel-wise frequency of occurrence with respect to laterality, sex, age, and pathologic grade.

Results: The 3-dimensional rendered images show that the tumors commonly located in the posterior cranial cavity, surrounding the tentorium. The posterior third of the superior sagittal sinus and the confluence of sinuses were commonly affected. According to the analysis of tumor occurrence frequency in the AAL template, IHPCs were mainly observed in the limbic lobe, occipital lobe, and cerebellum. Tumors in younger patients preferentially located in the right occipital region (P = .027), whereas those with higher pathological grade more often located in the left parietal lobe (P = .034).

Conclusions: This is the first voxel-based study to explore the predilection site of IHPCs. Our study suggests that these tumors commonly affect the posterior cranial cavity, adjoining the tentorium and venous sinus. Further research is needed to investigate the possible factors underlying these topographic preferences.
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http://dx.doi.org/10.1111/jon.12701DOI Listing
May 2020

Pre-treatment neutrophils count as a prognostic marker to predict chemotherapeutic response and survival outcomes in glioma: a single-center analysis of 288 cases.

Am J Transl Res 2020 15;12(1):90-104. Epub 2020 Jan 15.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University Beijing, China.

Background: Glioma is the most common and deadliest malignant primary intracranial brain tumor in adults. It remains unclear whether the pre-treatment peripheral blood test parameters might serve as biomarkers for treatment outcome. The purpose of the current study was to investigate the predictive and prognostic value of pre-treatment peripheral blood test parameters in glioma.

Methods: In total, 288 glioma patients with complete results of pre-operation peripheral blood test, clinical information and tumor transcriptome data from Chinese Glioma Genome Atlas (CGGA project) were enrolled in our study. Receiver operating characteristic (ROC) curve, Kaplan-Meier analysis and Cox proportional hazards models were performed to evaluate the diagnostic and prognostic value of pre-treatment peripheral blood test parameters in glioma patients.

Results: The white blood cells (WBC) and neutrophils (NEU) counts and neutrophil to lymphocyte ratio (NLR) were positively correlated with tumor grade. IDH mutation and 1p/19q codeletion occurred frequently in patients with higher NEU counts and NLR. We also found that glioma patients with higher NEU or NLR were more likely to have a significantly decreased overall survival. Meanwhile, NEU count was a prognostic marker for TMZ standard treatment GBM patients or IDH wild-type GBM patients. Further biological and functional analysis revealed that NEU count was positively associated with cell cycle and DNA duplication.

Conclusion: Our study was first to highlight the clinical significance of NEU count in GBM clinical treatment, which should be fully valued for clinical prediction and precise management.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013209PMC
January 2020

Predicting the likelihood of early recurrence based on mRNA sequencing of pituitary adenomas.

Gland Surg 2019 Dec;8(6):648-656

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China.

Background: There is no comprehensive and objective method existing for predicting early recurrence of pituitary adenomas (PAs). The most advanced gene sequencing technology can be applied to build a prognostic model that can effectively predict early recurrence of PAs.

Methods: In this study, using mRNA-Seq data, the corresponding postoperative early recurrence status, and other clinical features of 107 PA samples were obtained and randomly divided into the training and validation groups. Cox regression and receiver operating characteristic (ROC) analysis accompanied by the risk score method was used to build a seven-gene prediction model.

Results: Area under curve values was 0.857 in the training group, 0.936 in the validation group, and 0.848 in all patients. Patients with low-risk scores had a significantly lower probability of early postoperative recurrence compared to those acquiring high-risk scores in the training group, validation group, and all patient (P<0.0001) groups. In addition, 6 out of these 7 significant genes were highly correlated to the early recurrence of PAs.

Conclusions: This prediction model derived from mRNA-Seq data may help in identifying the early recurrence of PAs, consequently aiding in the classification of patients with PAs and the administration of the appropriate therapeutic and follow-up strategy for these patients.
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http://dx.doi.org/10.21037/gs.2019.11.02DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6989919PMC
December 2019

Development and validation of a candidate reference method for serum cortisol by isotope dilution liquid chromatography-tandem mass spectrometry combined with dextran sulfate-Mg precipitation.

Anal Bioanal Chem 2020 Feb 10;412(6):1325-1333. Epub 2020 Jan 10.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology, Beijing, P.R. China, No.1 DaHua Road, Dong Dan, Beijing, 100730, China.

Accurate and precise cortisol measurements are requisite for ensuring appropriate diagnosis and management of diseases related with adrenal or pituitary gland disorders. Prompted by the needs in characterization of certified reference materials and quality assurance for serum cortisol measurements, we developed and evaluated a highly reliable measurement procedure based on isotope dilution liquid chromatography-tandem mass spectrometry (ID LC-MS/MS) combined with dextran sulfate-Mg precipitation as the sample pretreatment. An appropriate amount of serum was accurately weighed and spiked with the isotope labelled internal standard. After precipitation, massive lipids and lipoproteins were removed from serum matrix. The clear supernatant was transferred and extracted with ethyl acetate-hexane solution. The cortisol was analyzed with LC-MS/MS in positive electrospray ionization mode. The within-run and total coefficient of variations (CVs) ranged from 0.3 to 0.6% and 0.7 to 1.2%, respectively, for a concentration range of 76.30 to 768.04 nmol/L. A regression comparison of the results obtained by the present method and the certified values of ERM-DA451 showed agreement with no statistical difference (Y = 1.0092 X-0.7455; 95% CI for the slope, 0.9940 to 1.0212; 95% CI for the intercept, - 3.6575 to 2.6390, r = 0.999). All structural analogs of cortisol tested were well resolved from cortisol in 12 min on a phenyl ligand column under an isocratic elution. The limit of quantification was estimated to 5 pg cortisol in absolute amount. This method is accurate and simple and can be served as a candidate reference measurement procedure in establishment of serum cortisol reference system.
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http://dx.doi.org/10.1007/s00216-019-02356-2DOI Listing
February 2020
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