Publications by authors named "Jinlong Shi"

100 Publications

Spatio-temporal evolution and influencing mechanism of the COVID-19 epidemic in Shandong province, China.

Sci Rep 2021 04 9;11(1):7811. Epub 2021 Apr 9.

College of Urban and Environmental Sciences, Northwest University, Xi'an, 710127, China.

The novel coronavirus pneumonia (COVID-19) outbreak that emerged in late 2019 has posed a severe threat to human health and social and economic development, and thus has become a major public health crisis affecting the world. The spread of COVID-19 in population and regions is a typical geographical process, which is worth discussing from the geographical perspective. This paper focuses on Shandong province, which has a high incidence, though the first Chinese confirmed case was reported from Hubei province. Based on the data of reported confirmed cases and the detailed information of cases collected manually, we used text analysis, mathematical statistics and spatial analysis to reveal the demographic characteristics of confirmed cases and the spatio-temporal evolution process of the epidemic, and to explore the comprehensive mechanism of epidemic evolution and prevention and control. The results show that: (1) the incidence rate of COVID-19 in Shandong is 0.76/100,000. The majority of confirmed cases are old and middle-aged people who are infected by the intra-province diffusion, followed by young and middle-aged people who are infected outside the province. (2) Up to February 5, the number of daily confirmed cases shows a trend of "rapid increase before slowing down", among which, the changes of age and gender are closely related to population migration, epidemic characteristics and intervention measures. (3) Affected by the regional economy and population, the spatial distribution of the confirmed cases is obviously unbalanced, with the cluster pattern of "high-low" and "low-high". (4) The evolution of the migration pattern, affected by the geographical location of Wuhan and Chinese traditional culture, is dominated by "cross-provincial" and "intra-provincial" direct flow, and generally shows the trend of "southwest → northeast". Finally, combined with the targeted countermeasures of "source-flow-sink", the comprehensive mechanism of COVID-19 epidemic evolution and prevention and control in Shandong is revealed. External and internal prevention and control measures are also figured out.
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http://dx.doi.org/10.1038/s41598-021-86188-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035406PMC
April 2021

Knowledge-aware multi-center clinical dataset adaptation: Problem, method, and application.

J Biomed Inform 2021 Mar 11;115:103710. Epub 2021 Feb 11.

College of Biomedical Engineering and Instrument Science, Zhejiang University, China. Electronic address:

Adaptable utilization of clinical data collected from multiple centers, prompted by the need to overcome the shifts between the dataset distributions, and exploit these different datasets for potential clinical applications, has received significant attention in recent years. In this study, we propose a novel approach to this task by infusing an external knowledge graph (KG) into multi-center clinical data mining. Specifically, we propose an adversarial learning model to capture shared patient feature representations from multi-center heterogeneous clinical datasets, and employ an external KG to enrich the semantics of the patient sample by providing both clinical center-specific and center-general knowledge features, which are trained with a graph convolutional autoencoder. We evaluate the proposed model on a real clinical dataset extracted from the general cardiology wards of a Chinese hospital and a well-known public clinical dataset (MIMIC III, pertaining to ICU clinical settings) for the task of predicting acute kidney injury in patients with heart failure. The achieved experimental results demonstrate the efficacy of our proposed model.
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http://dx.doi.org/10.1016/j.jbi.2021.103710DOI Listing
March 2021

R-Wave Singularity: A New Morphological Approach to the Analysis of Cardiac Electrical Dyssynchrony.

Front Physiol 2020 22;11:599838. Epub 2020 Dec 22.

Medical Innovation Research Division, Research Center for Biomedical Engineering, Chinese PLA General Hospital, Beijing, China.

R-wave singularity (RWS) measures the intermittence or discontinuousness of R waves. It has been broadly used in QRS (QRS complex of electrocardiogram) detection, electrocardiogram (ECG) beats classification, . In this article, we novelly developed RWS to the analysis of QRS morphology as the measurement of ventricular dyssynchrony and tested the hypothesis that RWS could enhance the discrimination between control and acute myocardial infarction (AMI) patients. Holter ECG recordings were obtained from the Telemetric and Holter ECG Warehouse database, among which database Normal was extracted as normal controls ( = 202) and database AMI ( = 93) as typical subjects of autonomic nervous system dysfunction and cardiac electrical dyssynchrony with high risk for cardiac arrhythmias and sudden cardiac death. Experimental results demonstrate that RWS measured by Lipschitz exponent calculated from 5-min Holter recordings was significantly less negative in early AMI and late AMI than that in Normal subjects for overall, elderly, and elderly male groups, which suggested the heterogeneous depolarization of the ventricular myocardium during AMI. Receiver operating characteristic curve analyses show that combined with heart rate variability parameters, Lipschitz exponent provides higher accuracy in distinguishing between the patients with AMI and healthy control subjects for overall, elderly, elderly male, and elderly female groups. In summary, our study demonstrates the significance of using RWS to probe the cardiac electrical dyssynchrony for AMI. Lipschitz exponent may be valuable and complementary for existing cardiac resynchronization therapy and autonomic nervous system assessment.
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http://dx.doi.org/10.3389/fphys.2020.599838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783454PMC
December 2020

Heart rhythm complexity as predictors for the prognosis of end-stage renal disease patients undergoing hemodialysis.

BMC Nephrol 2020 12 9;21(1):536. Epub 2020 Dec 9.

Research Center for Biomedical Engineering, Medical Innovation & Research Division, Chinese PLA General Hospital, Fuxing Road, Beijing, 100853, China.

Background: Heart rhythm complexity, a measure of heart rate dynamics and a risk predictor in various clinical diseases, has not been systematically studied in patients with end-stage renal disease. The aim of this study is to investigate the heart rhythm complexity and its prognostic value for mortality in end-stage renal disease patients undergoing hemodialysis.

Methods: To assess heart rhythm complexity and conventional heart rate variability measures, 4-h continuous electrocardiography for a retrospective cohort of 202 ostensibly healthy control subjects and 51 hemodialysis patients with end-stage renal disease were analyzed. Heart rhythm complexity was quantified by the complexity index from the measurement of the multiscale entropy profile.

Results: During a follow-up of 13 months, 8 people died in the patient group. Values of either traditional heart rate variability measurements or complexity indices were found significantly lower in patients than those in healthy controls. In addition, the complexity indices (Area 1-5, Area 6-15 and Area 6-20) in the mortality group were significantly lower than those in the survival group, while there were no significant differences in traditional heart rate variability parameters between the two groups. In receiver operating characteristic curve analysis, Area 6-20 (AUC = 0.895, p < 0.001) showed the strongest predictive power between mortality and survival groups.

Conclusion: The results suggest that heart rhythm complexity is impaired for patients with end-stage renal disease. Furthermore, the complexity index of heart rate variability quantified by multiscale entropy may be a powerful independent predictor of mortality in end-stage renal disease patients undergoing hemodialysis.
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http://dx.doi.org/10.1186/s12882-020-02196-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727237PMC
December 2020

A Routing-Based Repair Method for Digital Microfluidic Biochips Based on an Improved Dijkstra and Improved Particle Swarm Optimization Algorithm.

Micromachines (Basel) 2020 Nov 28;11(12). Epub 2020 Nov 28.

School of Mechatronics Engineering, Harbin Institute of Technology, Harbin 150001, China.

Digital microfluidic biochips (DMFBs) are attractive instruments for obtaining modern molecular biology and chemical measurements. Due to the increasingly complex measurements carried out on a DMFB, such chips are more prone to failure. To compensate for the shortcomings of the module-based DMFB, this paper proposes a routing-based fault repair method. The routing-based synthesis methodology ensures a much higher chip utilization factor by removing the virtual modules on the chip, as well as removing the extra electrodes needed as guard cells. In this paper, the routing problem is identified as a dynamic path-planning problem and mixed path design problem under certain constraints, and an improved Dijkstra and improved particle swarm optimization (ID-IPSO) algorithm is proposed. By introducing a cost function into the Dijkstra algorithm, the path-planning problem under dynamic obstacles is solved, and the problem of mixed path design is solved by redefining the position and velocity vectors of the particle swarm optimization. The ID-IPSO routing-based fault repair method is applied to a multibody fluid detection experiment. The proposed design method has a stronger optimization ability than the greedy algorithm. The algorithm is applied to , , and fault-free chips. The proposed ID-IPSO routing-based chip design method saves 13.9%, 14.3%, and 14.5% of the experiment completion time compared with the greedy algorithm. Compared with a modular fault repair method based on the genetic algorithm, the ID-IPSO routing-based fault repair method has greater advantages and can save 39.3% of the completion time on average in the completion of complex experiments. When the ratio of faulty electrodes is less than 12% and 23%, the modular and ID-IPSO routing-based fault repair methods, respectively, can guarantee a 100% failure repair rate. The utilization rate of the electrodes is 18% higher than that of the modular method, and the average electrode usage time is 17%. Therefore, the ID-IPSO routing-based fault repair method can accommodate more faulty electrodes for the same fault repair rate; the experiment completion time is shorter, the average number of electrodes is lower, and the security performance is better.
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http://dx.doi.org/10.3390/mi11121052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761094PMC
November 2020

Detecting Rare Variants and Heteroplasmy of Mitochondrial DNA from High-Throughput Sequencing in Patients with Coronary Artery Disease.

Med Sci Monit 2020 Nov 2;26:e925401. Epub 2020 Nov 2.

Core Laboratory of Translational Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China (mainland).

BACKGROUND Although mutations and dysfunction of mitochondrial DNA (mtDNA) are related to a variety of diseases, few studies have focused on the relationship between mtDNA and coronary artery disease (CAD), especially the relationship between rare variants and CAD. MATERIAL AND METHODS Two-stage high-throughput sequencing was performed to detect mtDNA variants or heteroplasmy and the relationship between them and CAD phenotypes. In the discovery stage, mtDNA was analyzed by high-throughput sequencing of long-range PCR products generated from the peripheral blood of 85 CAD patients and 80 demographically matched controls. In the validation stage, high-throughput sequencing for mtDNA target regions captured by GenCap Kit was performed on 100 CAD samples and 100 controls. Finally, tRNA fine mapping was performed between our study and the reported Chinese CAD study. RESULTS Among the tRNA genes, we confirmed a highly conserved rare variant, A5592G, previously reported in the Chinese CAD study, and 2 novel rare mutations that reached Bonferroni's correction significance in the combined analysis were found (P=7.39×10-4 for T5628C in tRNAAla and P=1.01×10-5 for T681C in 12S rRNA) in the CAD study. Both of them were predicted to be pathological, with T5628C disrupting an extremely conservative base-pairing at the AC stem of tRNAAla. Furthermore, we confirmed the controversial issue that the number of non-synonymous heteroplasmic sites per sample was significantly higher in CAD patients. CONCLUSIONS In conclusion, our study confirmed the contribution of rare variants in CAD and showed that CAD patients had more non-synonymous heterogeneity mutations, which may be helpful in identifying the genetic and molecular basis of CAD.
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http://dx.doi.org/10.12659/MSM.925401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646198PMC
November 2020

Matrix Metallopeptidase 14: A Candidate Prognostic Biomarker for Diffuse Large B-Cell Lymphoma.

Front Oncol 2020 20;10:1520. Epub 2020 Aug 20.

Department of Hematology, Chinese PLA General Hospital, Beijing, China.

Background: Matrix metallopeptidase 14 (MMP14) is an important gene in the regulation of T-cell function. However, the correlation between MMP14 expression, prognosis, and immune cell infiltration in diffuse large B-cell lymphoma (DLBCL) remains unclear.

Methods: We investigated the influence of MMP14 on clinical prognosis using data obtained from three Gene Expression Omnibus (GEO) database sets (GSE98588, GSE10846, and GSE4475). The expression of MMP14 was analyzed using the Gene Expression Profiling Interactive Analysis (GEPIA). The correlation between MMP14 and immune cell infiltration was investigated using the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Tumor Immune Estimation Resource (TIMER) tools. In addition, the correlation between MMP14 expression and immune gene markers was analyzed by TIMER and GEPIA.

Results: MMP14 expression positively correlated with favorable progression-free survival (PFS; GSE98588, = 0.02) and overall survival (OS; GSE98588, = 0.003; GSE10846, = 5.517e-05; and GSE4475, = 9.85e-04). Moreover, MMP14 expression was higher in DLBCL tumors than in normal tissues. Regarding clinical characteristics, high MMP14 expression was found to be correlated with race. MMP14 expression was also correlated with immune cell infiltration and had a remarkable correlation with various immune marker sets. It was found that M0 macrophages were the immune cells most related to survival, decreasing with the increase in Ann Arbor clinical stage. The results especially showed that MMP14 was a prognostic biomarker and related to the macrophages M0.

Conclusion: The results suggest that MMP14 is a novel prognostic molecular marker for DLBCL and is related to the immune cell infiltration, especially related to the macrophages M0. Our study provides insights for understanding the potential roles of MMP14 in tumor immunology and its suitability as a prognosis biomarker in DLBCL.
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http://dx.doi.org/10.3389/fonc.2020.01520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473157PMC
August 2020

A Novel RNA-Seq-Based Model for Preoperative Prediction of Lymph Node Metastasis in Oral Squamous Cell Carcinoma.

Biomed Res Int 2020 31;2020:4252580. Epub 2020 Aug 31.

Department of Stomatology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100853, China.

Objective: To develop and validate a novel RNA-seq-based nomogram for preoperative prediction of lymph node metastasis (LNM) for patients with oral squamous cell carcinoma (OSCC).

Methods: RNA-seq data for 276 OSCC patients (including 157 samples with LNM and 119 without LNM) were downloaded from TCGA database. Differential expression analysis was performed between LNM and non-LNM of OSCC. These samples were divided into a training set and a test set by a ratio of 9 : 1 while the relative proportion of the non-LNM and LNM groups was kept balanced within each dataset. Based on clinical features and seven candidate RNAs, we established a prediction model of LNM for OSCC using logistic regression analysis. Tenfold crossvalidation was utilized to examine the accuracy of the nomogram. Decision curve analysis was performed to evaluate the clinical utility of the nomogram.

Results: A total of 139 differentially expressed RNAs were identified between LNM and non-LNM of OSCC. Seven candidate RNAs were screened based on FPKM values, including NEURL1, AL162581.1 (miscRNA), AP002336.2 (lncRNA), CCBE1, CORO6, RDH12, and AC129492.6 (pseudogene). Logistic regression analysis revealed that the clinical N stage ( < 0.001) was an important factor to predict LNM. Moreover, three RNAs including RDH12 ( value < 0.05), CCBE1 ( value < 0.01), and AL162581.1 ( value < 0.05) could be predictive biomarkers for LNM in OSCC patients. The average accuracy rate of the model was 0.7661, indicating a good performance of the model.

Conclusion: Our findings constructed an RNA-seq-based nomogram combined with clinicopathology, which could potentially provide clinicians with a useful tool for preoperative prediction of LNM and be tailored for individualized therapy in patients with OSCC.
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http://dx.doi.org/10.1155/2020/4252580DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479460PMC
May 2021

Transcriptome-based drug repositioning for coronavirus disease 2019 (COVID-19).

Pathog Dis 2020 06;78(4)

Key Laboratory of Biomedical Engineering and Translational Medicine, Ministry of Industry and Information Technology, Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) around the world has led to a pandemic with high morbidity and mortality. However, there are no effective drugs to prevent and treat the disease. Transcriptome-based drug repositioning, identifying new indications for old drugs, is a powerful tool for drug development. Using bronchoalveolar lavage fluid transcriptome data of COVID-19 patients, we found that the endocytosis and lysosome pathways are highly involved in the disease and that the regulation of genes involved in neutrophil degranulation was disrupted, suggesting an intense battle between SARS-CoV-2 and humans. Furthermore, we implemented a coexpression drug repositioning analysis, cogena, and identified two antiviral drugs (saquinavir and ribavirin) and several other candidate drugs (such as dinoprost, dipivefrine, dexamethasone and (-)-isoprenaline). Notably, the two antiviral drugs have also previously been identified using molecular docking methods, and ribavirin is a recommended drug in the diagnosis and treatment protocol for COVID pneumonia (trial version 5-7) published by the National Health Commission of the P.R. of China. Our study demonstrates the value of the cogena-based drug repositioning method for emerging infectious diseases, improves our understanding of SARS-CoV-2-induced disease, and provides potential drugs for the prevention and treatment of COVID-19 pneumonia.
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http://dx.doi.org/10.1093/femspd/ftaa036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454646PMC
June 2020

High expression of AK1 predicts inferior prognosis in acute myeloid leukemia patients undergoing chemotherapy.

Biosci Rep 2020 06;40(6)

Department of Medicine, Huaihe Hospital of Henan University, Kaifeng 475000, China.

The purpose of the present study was to investigate whether expression levels of adenylate kinase 1 (AK1) were associated with prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). 85 AML patients with AK1 expression report who received chemotherapy-alone and 71 who underwent allo-HSCT from The Cancer Genome Atlas database were identified and grouped into either AK1high or AK1low based on their AK1 expression level relative to the median. Then, overall survival (OS) and event-free survival (EFS) were compared between patients with high vs. low AK1 expression. In the chemotherapy group, high AK1 expression was favorable for both EFS (P=0.016) and OS (P=0.014). In the allo-HSCT group, there was no association for AK1 expression levels and clinical outcomes. Further analyses suggested that in the high AK1 expression group, EFS and OS were longer in patients treated with allo-HSCT compared with those treated with chemotherapy (P=0.0011; P<0.0001, respectively), whereas no significant differences were observed in the low AK1 expression group. In summary, we reported AK1 as an independent unfavorable prognostic factor of AML patients undergoing chemotherapy, and its use could also facilitate clinical decision-making in selecting treatment for AML patients. Patients with high AK1 expression may be recommended for early allo-HSCT.
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http://dx.doi.org/10.1042/BSR20200097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300281PMC
June 2020

Upregulation of Glutamic-Oxaloacetic Transaminase 1 Predicts Poor Prognosis in Acute Myeloid Leukemia.

Front Oncol 2020 24;10:379. Epub 2020 Mar 24.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all < 0.05). Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high expression, age ≥60 years, white blood cell count ≥15 × 10/L, bone marrow blasts ≥70%, and or mutations (all < 0.05); but in the allo-HSCT group, the only independent risk factor for survival was high expression ( < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to expression were mainly concentrated in "hematopoietic cell lineage" and "leukocyte transendothelial migration" signaling pathways. Collectively, expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.
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http://dx.doi.org/10.3389/fonc.2020.00379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105742PMC
March 2020

Pathological Grade-Associated Transcriptome Profiling of lncRNAs and mRNAs in Gliomas.

Front Oncol 2020 10;10:253. Epub 2020 Mar 10.

Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair and Department of Neurosurgery, The Affiliated Hospital of Nantong University, Nantong, China.

The aim of the present study was to explore the expression profiles of lncRNAs and mRNAs in glioma patients and to elucidate any potential relationship between lncRNAs and mRNAs in glioma. High-throughput transcriptome sequencing of mRNAs and lncRNAs from six normal tissues and 16 glioma tissues (grade II, six cases; grade III, four cases; and grade IV, six cases) was performed. Series test of cluster (STC) analysis was used to screen significant trending models associated with glioma. Gene co-expression networks were constructed for the differentially expressed lncRNAs and mRNAs, and gene-ontology (GO) and pathway-enrichment analyses were further performed. Quantitative real-time PCR was performed to validate the five most differentially expressed lncRNAs and mRNAs. After filtering the raw sequencing data, we found 578 lncRNAs and 3,216 mRNAs that were significantly dysregulated in glioma (fold change ≥ 2, < 0.05). Twenty model profiles of lncRNA and 10 model profiles of mRNA were summarized, and three patterns of lncRNAs and two patterns of mRNAs were of clinical significance. Three gene co-expression networks between mRNAs and lncRNAs were built to clarify the relationship between lncRNAs and mRNAs in glioma. GO and pathway analyses indicated that the differentially expressed lncRNAs and mRNAs were enriched in several biological processes and signaling pathways associated with tumorigenesis. Both lncRNAs and mRNAs exhibited dynamic differential expression profiles that indicated their potential roles in different degrees of glioma malignancy. A series of bioinformatics analyses indicated that most of these lncRNAs and mRNAs are involved in important biological processes and pathways associated with the pathogenesis of glioma. These results provide potential directions and valuable resources for future investigations via the comprehensive integration of these lncRNAs and mRNAs.
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http://dx.doi.org/10.3389/fonc.2020.00253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076085PMC
March 2020

Prognostic role of SCAMP family in acute myeloid leukemia.

Pharmacogenomics J 2020 08 28;20(4):595-600. Epub 2020 Jan 28.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, 510260, Guangzhou, China.

Acute myeloid leukemia (AML) is a malignant disease of myeloid hematopoietic stem or progenitor cells characterized by abnormal proliferation of primary and immature myeloid cells in bone marrow and peripheral blood. Gene mutation and expression profiles can be used as prognosis predictors for different prognostic subgroups. Secretory carrier-associated membrane proteins (SCAMPs) are a multigenic family with five members and act as cell surface vectors in the post-Golgi recycling pathways in mammals. Nevertheless, the prognostic and clinical influence of SCAMP family has hardly ever been illustrated in AML. In our study, expression patterns of SCAMP family (SCAMP1-5) were analyzed in 155 AML patients which were extracted from the Cancer Genome Atlas database. In chemotherapy, only subgroup, higher SCAMP1 level was significantly associated with longer EFS and OS (all P = 0.002), and SCAMP1 was confirmed to be an independent favorable factor in un-transplanted patients by Multivariate analysis (all P < 0.05). Nevertheless, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment subgroup, none of the SCAMP genes had any effect on the clinical survival. Our study found that high expression level of SCAMP1 is a favorable prognostic factor in AML, but allo-HSCT may neutralize its prognostic effect.
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http://dx.doi.org/10.1038/s41397-020-0149-2DOI Listing
August 2020

Impacts of the Plateau Environment on the Gut Microbiota and Blood Clinical Indexes in Han and Tibetan Individuals.

mSystems 2020 Jan 21;5(1). Epub 2020 Jan 21.

Beijing Key Laboratory for Precision Medicine of Chronic Heart Failure, Chinese PLA General Hospital, Beijing, China

The intestinal microbiota is significantly affected by the external environment, but our understanding of the effects of extreme environments such as plateaus is far from adequate. In this study, we systematically analyzed the variation in the intestinal microbiota and 76 blood clinical indexes among 393 healthy adults with different plateau living durations (Han individuals with no plateau living, with plateau living for 4 to 6 days, with plateau living for >3 months, and who returned to the plain for 3 months, as well as plateau-living Tibetans). The results showed that the high-altitude environment rapidly (4 days) and continually (more than 3 months) shaped both the intestinal microbiota and clinical indexes of the Han population. With prolongation of plateau living, the general characteristics of the intestinal microbiota and clinical indexes of the Han population were increasingly similar to those of the Tibetan population. The intestinal microbiota of the Han population that returned to the plain area for 3 months still resembled that of the plateau-living Han population rather than that of the Han population on the plain. Moreover, clinical indexes such as blood glucose were significantly lower in the plateau groups than in the nonplateau groups, while the opposite result was obtained for testosterone. Interestingly, there were Tibetan-specific correlations between glucose levels and and abundance in the intestine. The results of this study suggest that a hypoxic environment could rapidly and lastingly affect both the human intestinal microbiota and blood clinical indexes, providing new insights for the study of plateau adaptability. The data presented in the present study demonstrate that the hypoxic plateau environment has a profound impact on the gut microbiota and blood clinical indexes in Han and Tibetan individuals. The plateau-changed signatures of the gut microbiota and blood clinical indexes were not restored to the nonplateau status in the Han cohorts, even when the individuals returned to the plain from the plateau for several months. Our study will improve the understanding of the great impact of hypoxic environments on the gut microbiota and blood clinical indexes as well as the adaptation mechanism and intervention targets for plateau adaptation.
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http://dx.doi.org/10.1128/mSystems.00660-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977073PMC
January 2020

High expression of chaperonin-containing TCP1 subunit 3 may induce dismal prognosis in multiple myeloma.

Pharmacogenomics J 2020 08 6;20(4):563-573. Epub 2020 Jan 6.

Department of Operations and Information Management, China-Japan Friendship Hospital, Beijing, 100029, China.

The prognosis role of CCT3 in MM and the possible pathways it involved were studied in our research. By analyzing ten independent datasets (including 48 healthy donors, 2220 MM, 73 MGUS, and 6 PCL), CCT3 was found to express higher in MM than healthy donors, and the expression level was gradually increased from MGUS, SMM, MM to PCL (all P < 0.01). By analyzing three independent datasets (GSE24080, GSE2658, and GSE4204), we found that CCT3 was a significant indicator of poor prognosis (all P < 0.01). KEGG and GSEA analysis showed that CCT3 expression was associated with JAK-STAT3 pathway, Hippo signaling pathway, and WNT signaling pathway. In addition, different expressed genes analysis revealed MYC, which was one of the downstream genes regulated by JAK-STAT3 pathway, was upregulated in MM. This confirms that JAK-STAT3 signaling pathway may promote the progress of disease which was regulated by CCT3 expression. Our study revealed that CCT3 may play a supporting role at the diagnosis of myeloid, and high expression of CCT3 suggested poor prognosis in MM. CCT3 expression may promote the progression of MM mainly by regulating MYC through JAK-STAT3 signaling pathway.
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http://dx.doi.org/10.1038/s41397-019-0145-6DOI Listing
August 2020

High expression of DOCK2 indicates good prognosis in acute myeloid leukemia.

J Cancer 2019 15;10(24):6088-6094. Epub 2019 Oct 15.

Department of Hematology, Huaihe Hospital of Henan University, Kaifeng, 475000, China.

DOCK family proteins are evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase with different cellular functions. It has been demonstrated that DOCK1 had adverse prognostic effect in acute myeloid leukemia (AML). We first analyzed data of 85 AML patients who were treated with chemotherapy and had available DOCK1 to DOCK11 expression information and found that DOCK1 and DOCK2 had prognostic significance in AML. In view of the known prognosis of DOCK1 in AML, we then explored the prognostic role of DOCK2. One hundred fifty-six AML patients with DOCK2 expression data were extracted from The Cancer Genome Atlas (TCGA) database and enrolled in this study. Patients were divided based on treatment modality into the chemotherapy group and the allogeneic hematopoietic stem cell transplant (allo-HSCT) group. Each group was divided into two groups by the median expression levels of DOCK2. In the chemotherapy group, high DOCK2 expression was associated with longer event-free survival (EFS, =0.001) and overall survival (OS, =0.007). In the allo-HSCT group, EFS and OS were not significantly different between high and low DOCK2 expression groups. Multivariate analysis showed that high DOCK2 expression was an independent favorable prognostic factor for both EFS and OS in all patients (all <0.05). In conclusion, our results indicated that high DOCK2 expression, in contrast to DOCK1, conferred good prognosis in AML.
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http://dx.doi.org/10.7150/jca.33244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856589PMC
October 2019

Up-regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia.

J Cell Mol Med 2020 01 21;24(1):1067-1075. Epub 2019 Nov 21.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event-free survival (EFS) than the low expressers among the chemotherapy-only group (all P < .001); EFS and OS were similar in the high and low DDIT4 expressers of the allogeneic haematopoietic stem cell transplantation (allo-HSCT) group. Furthermore, in the DDIT4 group, patients treated with allo-HSCT had longer EFS and OS than those who received chemotherapy alone (all P < .01). In the DDIT4 group, OS and EFS were similar in different treatment groups. Secondly, we analysed two other cytogenetically normal AML (CN-AML) cohorts derived from the Gene Expression Omnibus database, which confirmed that high DDIT4 expression was associated with poorer survival. Gene Ontology (GO) enrichment analysis showed that the genes related to DDIT4 expression were mainly concentrated in the acute and chronic myeloid leukaemia signalling pathways. Collectively, our study indicates that high DDIT4 expression may serve as a poor prognostic factor for AML, but its prognostic effects could be outweighed by allo-HSCT.
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http://dx.doi.org/10.1111/jcmm.14831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933361PMC
January 2020

Hypomethylation of 111 Probes Predicts Poor Prognosis for Glioblastoma.

Front Neurosci 2019 25;13:1137. Epub 2019 Oct 25.

National Engineering Laboratory for Medical Big Data Application Technology, Chinese PLA General Hospital, Beijing, China.

Glioblastoma (GBM) is a complicated brain tumor with heterogeneous outcome. Identification of effective biomarkers is an urgent need for the treatment decision-making and precise evaluation of prognosis. Based on a relatively large dataset of genome-wide methylation (138 glioblastoma patients), a joint-score of 111 methyl-probes was found to be of statistical significance for prognostic evaluation. Low joint-score were significantly associated with adverse outcomes (OS: < 0.001, PFS: = 0.03). Multivariable analyses adjusted for known risk factors confirmed the low joint-score of 111 methyl-probes as a high risk factor. The prognostic value of the methylated joint-score was further validated in another dataset of glioblastoma patients (OS: = 0.006). Additionally, variance analysis revealed that aberrant genetic and epigenetic alterations were significantly associated with the joint-score of those methyl-probes. In conclusion, our results supported the joint-score of 111 methyl-probes as a potential prognosticator for the precision treatment of glioblastoma.
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http://dx.doi.org/10.3389/fnins.2019.01137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823878PMC
October 2019

Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia.

Nat Commun 2019 11 7;10(1):5051. Epub 2019 Nov 7.

Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, 1098 Xueyuan Ave, 518060, Shenzhen, China.

The oncogenic fusion protein AML1-ETO retains the ability of AML1 to interact with the enhancer core DNA sequences, but blocks AML1-dependent transcription. Previous studies have shown that post-translational modification of AML1-ETO may play a role in its regulation. Here we report that AML1-ETO-positive patients, with high histone lysine methyltransferase Enhancer of zeste homolog 1 (EZH1) expression, show a worse overall survival than those with lower EZH1 expression. EZH1 knockdown impairs survival and proliferation of AML1-ETO-expressing cells in vitro and in vivo. We find that EZH1 WD domain binds to the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43). This requires the EZH1 SET domain, which augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation by point mutation or domain deletion impairs AML1-ETO-repressive activity. These findings highlight the role of EZH1 in non-histone lysine methylation, indicating that cooperation between AML1-ETO and EZH1 and AML1-ETO site-specific lysine methylation promote AML1-ETO transcriptional repression in leukemia.
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http://dx.doi.org/10.1038/s41467-019-12960-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838331PMC
November 2019

Expression level of ACOT7 influences the prognosis in acute myeloid leukemia patients.

Cancer Biomark 2019 ;26(4):441-449

Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, China.

Background: ACOT plays an important role in lipid metabolism and recent studies found that ACOT participates in some kinds of tumorigenesis. However, both the role of ACOT and its significance have not been revealed in AML. Therefore, we conduct this study in order to investigate the association between AML and ACOT, and hopefully contributed to the management of AML.

Methods: One hundred and fifty-six AML patients were enrolled in our study whose data were derived from the Cancer Genome Atlas database. There were 85 patients who received only chemotherapy and other 71 patients underwent allo-HSCT.

Results: Patients in high ACOT7 group had a significant lower EFS and OS, while patients in high versus low expression levels of other types of ACOT showed no significant difference on the outcome. High level of ACOT7 related with poor outcome in both chemotherapy-only group and HSCT group.

Conclusions: High expression level of ACOT7 indicates unfavorable outcome in AML patients. Allo-HSCT could not overcome the unfavorable effect of ACOT7 in these patients.
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http://dx.doi.org/10.3233/CBM-182287DOI Listing
June 2020

Prognostic value of the PDLIM family in acute myeloid leukemia.

Am J Transl Res 2019 15;11(9):6124-6131. Epub 2019 Sep 15.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University Guangzhou 510260, Guangdong, China.

Acute myeloid leukemia (AML) is a genetically complex, highly aggressive hematological malignancy. Prognosis is usually with grim. PDZ and LIM domain proteins (PDLIM) are involved in the regulation of a variety of biological processes, including cytoskeletal organization, cell differentiation, organ development, neural signaling or tumorigenesis. The clinical and prognostic value of the PDLIM family in AML is unclear. To understand the role of PDLIM expression in AML, The Cancer Genome Atlas (TCGA) database was screened and 155 de novo AML patients with complete clinical information and the expression data of the PDLIM family were included in the study. The clinical and molecular characteristics associated with the expression of different members of the PDLIM family were summarized using various statistical methods. In 84 patients who only received chemotherapy, univariate analysis indicated that high expression of PDLIM2 or PDLIM7 was associated with shorter EFS and OS (both P<0.05 for PDLIM2, and both P<0.01 for PDLIM7). Multivariate analysis suggested that high expression of PDLIM7 was an independent risk factor for EFS and OS (both P<0.05). In the other 71 patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), survival was unaffected by PDLIM expressions. In summary, high expression of and , especially the latter, could serve as adverse prognostic factors for AML, but their prognostic effects could be reversed by allo-HSCT.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789254PMC
September 2019

Time-Course Transcriptome Analysis for Drug Repositioning in -Infected Human Gingival Fibroblasts.

Front Cell Dev Biol 2019 20;7:204. Epub 2019 Sep 20.

Department of Human Microbiome, School and Hospital of Stomatology, Shandong University and Shandong Provincial Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan, China.

() is a crucial periodontal pathogen and human gingival fibroblasts (GFs) are the first line of defense against oral pathogens. However, the research on potential molecular mechanisms of host defense and effective treatment of infection in GFs remains scarce. In this study, we undertook a time-series experiment and performed an RNA-seq analysis to explore gene expression profiles during the process of infection in GFs. Differentially expressed genes (DEGs) could be divided into three coexpression clusters. Functional analysis revealed that the immune-related signaling pathways were more overrepresented at the early stage, while metabolic pathways were mainly enriched at the late stage. We computationally identified several U.S. Food and Drug Administration (FDA)-approved drugs that could protect the infected GFs via a coexpression-based drug repositioning approach. Biologically, we confirmed that six drugs (etravirine, zalcitabine, wortmannin, calcium D-pantothenate, ellipticine, and tanespimycin) could significantly decrease -induced reactive oxygen species (ROS) generation and block the Protein Kinase B (PKB/AKT)/mitogen-activated protein kinase signaling pathways. Our study provides more detailed molecular mechanisms of the process by which infects GFs and illustrates the value of the cogena-based drug repositioning method and the potential therapeutic application of these tested drugs in the treatment of infection.
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http://dx.doi.org/10.3389/fcell.2019.00204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6771468PMC
September 2019

High Expression Levels of and Indicate Unfavorable Prognosis in Acute Myeloid Leukemia.

J Cancer 2019 10;10(18):4286-4292. Epub 2019 Jul 10.

Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing, 100191, China.

: Actinins are major cytoskeletal proteins that mediate sarcomere function, and they also have important non-muscle functions such as regulating cytokinesis, cell adhesion and migration. There are four isoforms of actinins in mammals (ACTN1-4). Recently, the relationship between actinins and cancer has been discovered in many types of malignancy, yet their prognostic significance in acute myeloid leukemia (AML) remains unclear. : We collected data of 155 de novo AML patients from The Cancer Genome Atlas (TCGA) database; 85 patients received chemotherapy only and 70 patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We divided each treatment groups into sub-groups based on the median expression levels of . : Survival analysis showed that in the chemotherapy-only group, high and expression were associated with shorter event-free survival (EFS) and overall survival (OS) (p<0.01). Multivariate analysis suggested that high expression of and (p<0.05) were independent poor prognostic factors. In the allo-HSCT group, expression had no impact on survival. : Our study suggested that high expression levels of and adversely affected the survival of AML patients, but their harmful impact could be overcome by allo-HSCT.
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http://dx.doi.org/10.7150/jca.31766DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691690PMC
July 2019

Prognostic significance of the family expression in acute myeloid leukemia.

Ann Transl Med 2019 Jun;7(12):261

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.

Background: Acute myeloid leukemia (AML) is a highly heterogenous hematological malignancy and its prognostication depends on the genetic mutation and expression profile of each patient. Pantothenate kinase () is a regulatory enzyme that controls coenzyme A (CoA) biosynthesis. It has four isoforms encoded by , respectively. Whether the expression of the family has prognostic significance in AML remains unclear.

Methods: We screened The Cancer Genome Atlas database for AML patients with complete expression data. Eighty-four AML patients met the criteria and were included in this study. Clinical characteristics at diagnosis, including peripheral blood (PB) white blood cell counts (WBC), blast percentages in PB and bone marrow (BM), French-American-British (FAB) subtypes and the frequencies of common genetic mutations were described. Survival was estimated using the Kaplan-Meier method and the log-rank test. Multivariate Cox proportional hazard models were constructed for event-free survival (EFS) and overall survival (OS), using a limited backward elimination procedure.

Results: Patients with high expression had significantly longer event-free survival (EFS) and overall survival (OS) than patients with low expression (P=0.007, P=0.016, respectively), whereas patients with high expression had shorter EFS and OS than patients with low expression (P=0.022, P=0.015, respectively). Multivariate analysis confirmed that high expression was an independent risk factor for EFS and OS (both P<0.05).

Conclusions: Our study suggested that high expression might have favorable effects on AML, while high expression was indicative of poor prognosis.
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http://dx.doi.org/10.21037/atm.2019.05.28DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6614324PMC
June 2019

High expression may predict poor prognosis in acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Cancer Biol Ther 2019 15;20(10):1314-1318. Epub 2019 Jul 15.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University , Guangzhou , China.

Epithelial growth factor-like 7 (EGFL7) is a secretory protein with a well-characterized role in angiogenesis and the oncogenesis of certain solid tumors. Overexpression of is associated with adverse prognosis in patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, whether this association persists after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. To further clarify the prognostic role of , seventy-one AML patients with expression data who underwent allo-HSCT from The Cancer Genome Atlas database were included and divided into either or group based on the median expression level. Two groups had similar clinical and molecular characteristics except that the group had less frequent mutations (= .001). Kaplan-Meier survival curves showed that high expressers had shorter OS than the low expressers (= .040). Univariate analysis showed that high expression, and mutations were associated with short OS (all < .05). Multivariate analysis indicated that high expression, and mutations were independent risk factors for OS (all < .05). Collectively, our study suggested that , like the other widely-used risk stratification factors, could serve as a prognostic tool and therapeutic target in AML, even after allo-HCST.
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http://dx.doi.org/10.1080/15384047.2019.1638663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783118PMC
August 2020

Emerging agents and regimens for treatment of relapsed and refractory acute myeloid leukemia.

Cancer Gene Ther 2020 02 11;27(1-2):1-14. Epub 2019 Jul 11.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Relapsed and refractory acute myeloid leukemia (R/R AML) has complicated pathogenesis. Its treatment is complicated, and the prognosis is poor. So far, there is no consensus on what is the optimal treatment strategy. With the deepening of research, new chemotherapy regimens, new small molecule inhibitors, and immunotherapy have been increasingly applied to clinical trials, providing more possibilities for the treatment of R/R AML. The most effective treatment for patients who achieve complete remission after recurrence is still sequential conditioning therapy followed by allogeneic hematopoietic cell transplantation. Finding the best combination of treatments is still an important goal for the future.
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http://dx.doi.org/10.1038/s41417-019-0119-5DOI Listing
February 2020

Prognostic value of the FUT family in acute myeloid leukemia.

Cancer Gene Ther 2020 02 17;27(1-2):70-80. Epub 2019 Jun 17.

Department of Hematology, The Second Affiliated Hospital of Guangzhou Medical University, 510260, Guangzhou, China.

Genetic abnormalities are more frequently viewed as prognostic markers in acute myeloid leukemia (AML) in recent years. Fucosylation, catalyzed by fucosyltransferases (FUTs), is a post-translational modification that widely exists in cancer cells. However, the expression and clinical implication of the FUT family (FUT1-11) in AML has not been investigated. From the Cancer Genome Atlas database, a total of 155 AML patients with complete clinical characteristics and FUT1-11 expression data were included in our study. In patients who received chemotherapy alone showed that high expression levels of FUT3, FUT6, and FUT7 had adverse effects on event-free survival (EFS) and overall survival (OS) (all P < 0.05), whereas high FUT4 expression had favorable effects on EFS and OS (all P < 0.01). However, in the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group, we only found a significant difference in EFS between the high and low FUT3 expression subgroups (P = 0.047), while other FUT members had no effect on survival. Multivariate analysis confirmed that high FUT4 expression was an independent favorable prognostic factor for both EFS (HR = 0.423, P = 0.001) and OS (HR = 0.398, P < 0.001), whereas high FUT6 expression was an independent risk factor for both EFS (HR = 1.871, P = 0.017) and OS (HR = 1.729, P = 0.028) in patients who received chemotherapy alone. Moreover, we found that patients with low FUT4 and high FUT6 expressions had the shortest EFS and OS (P < 0.05). Our study suggests that high expressions of FUT3/6/7 predict poor prognosis, high FUT4 expression indicates good prognosis in AML; FUT6 and FUT4 have the best prognosticating profile among them, but their effects could be neutralized by allo-HSCT.
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http://dx.doi.org/10.1038/s41417-019-0115-9DOI Listing
February 2020

High expression of microRNA-500 is associated with poor prognosis in patients with acute myeloid leukemia receiving allogeneic hematopoietic stem cell transplantation.

Oncol Lett 2019 Jun 15;17(6):5815-5820. Epub 2019 Apr 15.

Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, P.R. China.

MicroRNA-500 (miR-500) is a potential prognostic biomarker in a number of different types of cancer, such as prostate cancer and hepatocellular carcinoma. This study aimed to explore the clinical implications of miR-500 expression status in patients with acute myeloid leukemia (AML) that had received allogeneic hematopoietic stem cell transplantation (allo-HSCT). miR-500 expression status and clinical data were obtained from 74 patients with AML in the The Cancer Genome Atlas database receiving allo-HSCT. Patients with low expression level of miR-500 (miR-500) were significantly more likely to present with a French-American-British classification M2 subtype (P=0.003), and less likely to have the M5 subtype (P=0.040) compared with patients with high expression levels (miR-500). miR-500 patients were associated with low-risk AML (P=0.003) and core-binding factor subunit b-myosin heavy chain 11 translocation mutation (P=0.021). There was a significant difference in nucleophosmin 1 (P=0.009), NRAS proto-oncogene GTPase/KRAS proto-oncogene GTPase (P=0.047) and PHD finger protein 6 (P=0.040) expression levels between the two groups. miR-500 patients had a decreased overall survival (OS) time compared with the low expression group (P=0.035). Multivariate analysis revealed that miR-500 expression significantly affected OS time independent of other classical prognostic factors, such as age and common mutations. The analysis of survival curves further substantiated this result. The results obtained in the current study suggested that miR-500 may be a suitable prognostic marker for patients with AML receiving allo-HSCT.
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http://dx.doi.org/10.3892/ol.2019.10250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507407PMC
June 2019

MicroRNA-425 upregulation indicates better prognosis in younger acute myeloid leukemia patients undergoing chemotherapy.

Oncol Lett 2019 Jun 4;17(6):5793-5802. Epub 2019 Apr 4.

Department of Hematology and Lymphoma Research Center, Peking University, Third Hospital, Beijing 100191, P.R. China.

The aim of the present study was to investigate whether the expression levels of microRNA-425 (miR-425) were associated with the prognosis of acute myeloid leukemia (AML) in patients treated with chemotherapy or allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 162 AML patients were enrolled and divided into chemotherapy and allo-HSCT groups. Next, the overall survival (OS) and event-free survival (EFS) were compared between patients with high and low miR-425 expression in each of the treatment groups. In the chemotherapy group, high miR-425 expression was favorable for EFS (P=0.001) and OS (P=0.001) in younger patients (<60 years), whereas it had no effect on EFS and OS in older patients (≥60 years). In the allo-HSCT group, there was no association between miR-425 expression levels and clinical outcomes. Further analyses suggested that in the low miR-425 expression group, EFS and OS were longer in patients treated with allo-HSCT as compared with those treated with chemotherapy (both P<0.001), whereas no significant differences were observed in the high miR-425 expression group. In conclusion, the current data indicated that miR-425 is an independent favorable prognostic factor for younger AML patients undergoing chemotherapy, and its use may facilitate clinical decision-making in selecting treatment for AML patients. Patients with low miR-425 expression may benefit from allo-HSCT, whereas allo-HSCT did not appear to be beneficial in patients with high miR-425 expression.
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http://dx.doi.org/10.3892/ol.2019.10217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507333PMC
June 2019