Publications by authors named "Hao Cai"

339 Publications

Deep learning for differential diagnosis of malignant hepatic tumors based on multi-phase contrast-enhanced CT and clinical data.

J Hematol Oncol 2021 Sep 26;14(1):154. Epub 2021 Sep 26.

Department of Transplantation, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

Background: Liver cancer remains the leading cause of cancer death globally, and the treatment strategies are distinct for each type of malignant hepatic tumors. However, the differential diagnosis before surgery is challenging and subjective. This study aims to build an automatic diagnostic model for differentiating malignant hepatic tumors based on patients' multimodal medical data including multi-phase contrast-enhanced computed tomography and clinical features.

Methods: Our study consisted of 723 patients from two centers, who were pathologically diagnosed with HCC, ICC or metastatic liver cancer. The training set and the test set consisted of 499 and 113 patients from center 1, respectively. The external test set consisted of 111 patients from center 2. We proposed a deep learning model with the modular design of SpatialExtractor-TemporalEncoder-Integration-Classifier (STIC), which take the advantage of deep CNN and gated RNN to effectively extract and integrate the diagnosis-related radiological and clinical features of patients. The code is publicly available at https://github.com/ruitian-olivia/STIC-model .

Results: The STIC model achieved an accuracy of 86.2% and AUC of 0.893 for classifying HCC and ICC on the test set. When extended to differential diagnosis of malignant hepatic tumors, the STIC model achieved an accuracy of 72.6% on the test set, comparable with the diagnostic level of doctors' consensus (70.8%). With the assistance of the STIC model, doctors achieved better performance than doctors' consensus diagnosis, with an increase of 8.3% in accuracy and 26.9% in sensitivity for ICC diagnosis on average. On the external test set from center 2, the STIC model achieved an accuracy of 82.9%, which verify the model's generalization ability.

Conclusions: We incorporated deep CNN and gated RNN in the STIC model design for differentiating malignant hepatic tumors based on multi-phase CECT and clinical features. Our model can assist doctors to achieve better diagnostic performance, which is expected to serve as an AI assistance system and promote the precise treatment of liver cancer.
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http://dx.doi.org/10.1186/s13045-021-01167-2DOI Listing
September 2021

Estimation of pollutant sources in multi-zone buildings through different deconvolution algorithms.

Build Simul 2021 Sep 10:1-14. Epub 2021 Sep 10.

College of Electrical Engineering and Control Science, Nanjing Tech University, Nanjing, 210009 China.

Effective identification of pollution sources is particularly important for indoor air quality. Accurate estimation of source strength is the basis for source effective identification. This paper proposes an optimization method for the deconvolution process in the source strength inverse calculation. In the scheme, the concept of time resolution was defined, and combined with different filtering positions and filtering algorithms. The measures to reduce effects of measurement noise were quantitatively analyzed. Additionally, the performances of nine deconvolution inverse algorithms under experimental and simulated conditions were evaluated and scored. The hybrid algorithms were proposed and compared with single algorithms including Tikhonov regularization and iterative methods. Results showed that for the filtering position and algorithm, Butterworth filtering performed better, and different filtering positions had little effect on the inverse calculation. For the calculation time step, the optimal (time resolution) was 0.667% and 1.33% in the simulation and experiment, respectively. The hybrid algorithms were found to not perform better than the single algorithms, and the SART (simultaneous algebraic reconstruction technique) algorithm from CAT (computer assisted tomography) yielded better performances in the accuracy and stability of source strength identification. The relative errors of the inverse calculation for source strength were typically below 25% using the optimization scheme.
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http://dx.doi.org/10.1007/s12273-021-0826-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443894PMC
September 2021

Enhanced chemo-photodynamic therapy of an enzyme-responsive prodrug in bladder cancer patient-derived xenograft models.

Biomaterials 2021 Aug 27;277:121061. Epub 2021 Aug 27.

Department of Urology, Institute of Urology, Huaxi MR Research Center (HMRRC), National Clinical Research Center for Geriatrics, Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:

Patient-derived xenograft (PDX) models are powerful tools for understanding cancer biology and drug discovery. In this study, a polymeric nano-sized drug delivery system poly (OEGMA)[email protected] ([email protected]) composed of a photosensitizer chlorin e6 (Ce6) and a cathepsin B-sensitive polymer-paclitaxel (PTX) prodrug was constructed. The photochemical internalization (PCI) effect and enhanced chemo-photodynamic therapy (PDT) were achieved via a two-stage light irradiation strategy. The results showed that the [email protected] had great tumor targeting and rapid cellular uptake induced by PCI, thereby producing excellent anti-tumor effects on human bladder cancer PDX models with tumor growth inhibition greater than 98%. Bioinformatics analysis revealed that the combination of PTX chemotherapy and PDT up-regulated oxidative phosphorylation and reactive oxygen species (ROS) generation, blocked cell cycle and proliferation, and down-regulated the pathways related to tumor progression, invasion and metastasis, including hypoxia, TGF-β signaling and TNF-α signaling pathways. Western blots analysis confirmed that proteins promoting apoptosis (Bax, Cleaved caspase-3, Cleaved PARP) and DNA damage (γH2A.X) were up-regulated, while those inhibiting apoptosis (Bcl-2) and mitosis (pan-actin and α/β-tubulin) were down-regulated after chemo-PDT treatment. Therefore, this stimuli-responsive polymer-PTX prodrug-based nanomedicine with combinational chemotherapy and PDT evaluated in the PDX models could be a potential candidate for bladder cancer therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121061DOI Listing
August 2021

Fabrication of magnetic [email protected] composite and efficient removal of metronidazole by the photo-Fenton process in a wide pH range.

J Environ Manage 2021 Sep 8;300:113677. Epub 2021 Sep 8.

College of Chemistry and Material Sciences, Hebei Normal University, Shijiazhuang, China.

CuFeO-coated pretreated biochars ([email protected]) were synthesized for the first time via a facile method by impregnating and calcinating Cu-Fe-ethanol solution to activate HO for the degradation of metronidazole (MNZ) at a wide pH range. [email protected] samples were characterized by XRD, SEM, VSM, XPS, and BET. The results showed that CuFeO coating, which is evenly distributed on the surface of HNO-pretreated biochar, can provide more active sites to enable [email protected] to be activated by visible light. The introduction of biochar by impregnating and calcinating method effectively suppressed the aggregation of CuFeO and maintained its high surface area and pore structure. [email protected] composite can be separated easily by an external magnetic field. The PBC-400CuFe sample calcined under 400 °C showed superior photo-Fenton catalytic ability in MNZ degradation at a wide pH range (pH = 3-7) and exhibited high-efficiency degradation of about 96.3% with the dosage concentration of catalyst 0.4 g/L in the presence of HO at pH 3.0 within 60 min. While, at pH 7.0, the PBC-400CuFe material removed 91.1% MNZ within 120 min, and the degradation efficiency was still higher than that of traditional Fenton reaction and some Fenton-like reaction. The PBC-400CuFe showed good stability. After 5 times of repeated use, its removal rate was still above 89.1%. This study confirmed that O• and h are both important radicals, but the •OH played a key role in the visible photo/[email protected] H₂O₂ system. The results indicate that [email protected] is highly suitable for the wastewaters with high MNZ content under mild conditions.
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http://dx.doi.org/10.1016/j.jenvman.2021.113677DOI Listing
September 2021

Treatment and outcomes of POEMS syndrome: changes in the past 20 years.

Blood Cancer J 2021 Aug 14;11(8):145. Epub 2021 Aug 14.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.

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http://dx.doi.org/10.1038/s41408-021-00540-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364551PMC
August 2021

Bortezomib plus dexamethasone as first-line therapy for patients with POEMS syndrome.

Ann Hematol 2021 Jul 31. Epub 2021 Jul 31.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare plasma cell dyscrasia without standard front-line treatment. Merely, few studies have reported the responses and outcomes of bortezomib plus dexamethasone (BDex) in POEMS syndrome. In this study, a total of 69 patients (40 males) treated with front-line BDex were included. The median age at diagnosis was 50 years (range, 30-78 years). After a median of 9 cycles BDex (range 1-9), fifty-two (88.1%), thirty-two (46.4%), and forty-seven (71.2%) patients achieved the best neurologic response, hematological complete response, and serum vascular endothelial growth factor (VEGF) response, respectively. The extravascular overload, pulmonary hypertension, and renal impairment also substantially improved. No treatment-related death occurred. Two patients developed grade-1 bortezomib-induced peripheral neuropathy and were reversible after drug withdrawal. After a median follow-up of 22.5 months, the estimated 2-year overall survival and time to next treatment were 95.7% and 65.6%, respectively. In conclusion, the combination of bortezomib and dexamethasone is effective, with a high response rate and safety profile for patients with newly diagnosed POEMS syndrome.
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http://dx.doi.org/10.1007/s00277-021-04609-6DOI Listing
July 2021

Defects in Macrophage Reprogramming in Cancer Therapy: The Negative Impact of PD-L1/PD-1.

Front Immunol 2021 23;12:690869. Epub 2021 Jun 23.

Department of Transplantation, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Classically activated M1 macrophages and alternatively activated M2 macrophages are two polarized subsets of macrophages at the extreme ends of a constructed continuum. In the field of cancer research, M2 macrophage reprogramming is defined as the repolarization of pro-tumoral M2 to anti-tumoral M1 macrophages. It is known that colony-stimulating factor 1 (CSF1)/CSF1 receptor (CSF1R) and CSF2/CSF2R signaling play important roles in macrophage polarization. Targeting CSF1/CSF1R for M2 macrophage reprogramming has been widely performed in clinical trials for cancer therapy. Other targets for M2 macrophage reprogramming include Toll-like receptor 7 (TLR7), TLR8, TLR9, CD40, histone deacetylase (HDAC), and PI3Kγ. Although macrophages are involved in innate and adaptive immune responses, M1 macrophages are less effective at phagocytosis and antigen presenting, which are required properties for the activation of T cells and eradication of cancer cells. Similar to T and dendritic cells, the "functionally exhausted" status might be attributed to the high expression of programmed death-ligand 1 (PD-L1) or programmed cell death protein 1 (PD-1). PD-L1 is expressed on both M1 and M2 macrophages. Macrophage reprogramming from M2 to M1 might increase the expression of PD-L1, which can be transcriptionally activated by STAT3. Macrophage reprogramming or PD-L1/PD-1 blockade alone is less effective in the treatment of most cancers. Since PD-L1/PD-1 blockade could make up for the defect in macrophage reprogramming, the combination of macrophage reprogramming and PD-L1/PD-1 blockade might be a novel treatment strategy for cancer therapy.
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http://dx.doi.org/10.3389/fimmu.2021.690869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260839PMC
June 2021

Efficiency-Tunable Single-Component White-Light Emission Realized in Hybrid Halides Through Metal Co-Occupation.

ACS Appl Mater Interfaces 2021 Jun 15. Epub 2021 Jun 15.

The Beijing Municipal Key Laboratory of New Energy Materials and Technologies, School of Materials Sciences and Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Organic-inorganic hybrid metal halides have attracted widespread attention as emerging optoelectronic materials, especially in solid-state lighting, where they can be used as single-component white-light phosphors for white light-emitting diodes. Herein, we have successfully synthesized a zero-dimensional (0D) organic-inorganic hybrid mixed-metal halide (Bmpip)PbSnBr (0 < < 1, Bmpip = 1-butyl-1-methyl-piperidinium, CHN) that crystallizes in a monoclinic system in the 2/ space group. Pb and Sn form a four-coordinate seesaw structure separated by organic cations forming a 0D structure. For different excitation wavelengths, (Bmpip)PbSnBr (0 < < 1) exhibits double-peaked emission at 470 and 670 nm. The emission color of (Bmpip)PbSnBr can be easily tuned from orange-red to blue by adjusting the Pb/Sn molar ratio or excitation wavelength. Representatively, (Bmpip)PbSnBr exhibits approximately white-light emission with high photoluminescence quantum yield up to 39%. Interestingly, the color of (Bmpip)PbSnBr can also be easily tuned by temperature, promising its potential for application in temperature measurement and indication. Phosphor-converted light-emitting diodes are fabricated by combining (Bmpip)PbSnBr and 365 nm near-UV LED chips and exhibit high-quality light output.
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http://dx.doi.org/10.1021/acsami.1c07636DOI Listing
June 2021

Dynamics of the SARS-CoV-2 antibody response up to 10 months after infection.

Cell Mol Immunol 2021 07 7;18(7):1832-1834. Epub 2021 Jun 7.

Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1038/s41423-021-00708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182358PMC
July 2021

Investigation of PVT-Aware STT-MRAM Sensing Circuits for Low-VDD Scenario.

Micromachines (Basel) 2021 May 12;12(5). Epub 2021 May 12.

National ASIC System Engineering Center, Southeast University, Nanjing 210096, China.

Spintronic based embedded magnetic random access memory (eMRAM) is becoming a foundry validated solution for the next-generation nonvolatile memory applications. The hybrid complementary metal-oxide-semiconductor (CMOS)/magnetic tunnel junction (MTJ) integration has been selected as a proper candidate for energy harvesting, area-constraint and energy-efficiency Internet of Things (IoT) systems-on-chips. Multi-VDD (low supply voltage) techniques were adopted to minimize energy dissipation in MRAM, at the cost of reduced writing/sensing speed and margin. Meanwhile, yield can be severely affected due to variations in process parameters. In this work, we conduct a thorough analysis of MRAM sensing margin and yield. We propose a current-mode sensing amplifier (CSA) named 1D high-sensing 1D margin, high 1D speed and 1D stability (HMSS-SA) with reconfigured reference path and pre-charge transistor. Process-voltage-temperature (PVT) aware analysis is performed based on an MTJ compact model and an industrial 28 nm CMOS technology, explicitly considering low-voltage (0.7 V), low tunneling magnetoresistance (TMR) (50%) and high temperature (85 °C) scenario as the worst sensing case. A case study takes a brief look at sensing circuits, which is applied to in-memory bit-wise computing. Simulation results indicate that the proposed high-sensing margin, high speed and stability sensing-sensing amplifier (HMSS-SA) achieves remarkable performance up to 2.5 GHz sensing frequency. At 0.65 V supply voltage, it can achieve 1 GHz operation frequency with only 0.3% failure rate.
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http://dx.doi.org/10.3390/mi12050551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151166PMC
May 2021

Chrysin Stimulates Subcutaneous Fat Thermogenesis in Mice by Regulating PDGFRα and MicroRNA Expressions.

J Agric Food Chem 2021 Jun 24;69(21):5897-5906. Epub 2021 May 24.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.

The activation of adipose tissue browning and thermogenesis provides a new strategy to counter obesity and associated metabolic diseases. Here, a natural flavonoid chrysin is used as the supplement of a high-fat diet (HFD). Dietary chrysin alleviates adiposity and insulin resistance in HFD-fed mice. Meanwhile, dietary chrysin elevates systemic energy expenditure and enhances the uncoupling protein-1 (UCP1) level in subcutaneous adipose tissue (SAT), which is accompanied by the increased thermogenic program, beige preadipocyte number, and angiogenesis in SAT. Dietary chrysin also induces the expression of SAT platelet-derived growth factor receptor α (PDGFRα), which commits adipose progenitor cells to differentiate into beige or white adipocytes in response to various environmental signals. Double immunofluorescent staining for UCP1 and PDGFRα reveals that chrysin elevates the number of UCP1PDGFRα beige progenitors in SAT. Further, chrysin treatment reverses the effects of the specific PDGFRα inhibitor imatinib on browning differentiation of stromal vascular fraction cells from SAT. Finally, chrysin-induced adipocyte browning is correlated with the expressions of microRNAs as PDGFRα inhibitors or thermogenesis suppressors. In conclusion, dietary chrysin promotes subcutaneous adipocyte browning and systematic energy expenditure by regulating PDGFRα and microRNA expressions in HFD-fed mice.
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http://dx.doi.org/10.1021/acs.jafc.1c01130DOI Listing
June 2021

The seed oil of ameliorates Aβ25-35-induced Alzheimer's disease in rats.

Food Sci Nutr 2021 May 30;9(5):2402-2413. Epub 2021 Mar 30.

TAAHC-SWU Medicinal Plant Joint R&D Centre Tibetan Collaborative Innovation Centre of Agricultural and Animal Husbandry Resources Food Science College Tibet Agricultural and Animal Husbandry University Nyingchi China.

, a plant of the Paeoniaceae family, has abundant genetic diversity in different populations, and the seed oil can be used in a diverse number of activities. However, its neuroprotective effect is not clear. We investigated the memory-improving effects and associated mechanisms of seed oil (PLSO) on amyloid beta (Aβ)25-35-induced Alzheimer's disease (AD) in rats. The Morris water maze test was undertaken, and subsequently, the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and acetylcholinesterase (ACHE) in the hippocampus was detected by biochemical analyses. To further study PLSO, we examined the pathologic structure and apoptosis of hippocampal tissue by staining. Immunohistochemical analysis was used to detect expression of IBA-1 and GFAP in the hippocampus. Detection of proinflammatory factors was achieved by reverse transcription-quantitative polymerase chain reaction and Western blotting. High-dose PLSO inhibited expression of GFAP and IBA-1. We demonstrated that high-dose PLSO can regulate activation of glial cells and mediate apoptosis of hippocampal cells, and significantly improve learning and memory deficits in AD rats. PLSO could be developed as a nutritional supplement and sold as a drug for AD prevention and/or treatment.
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http://dx.doi.org/10.1002/fsn3.2102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116862PMC
May 2021

Mir-139-5p inhibits glioma cell proliferation and progression by targeting GABRA1.

J Transl Med 2021 05 17;19(1):213. Epub 2021 May 17.

Department of Neurosurgery, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, No.283 Tongzipo road, Yuelu district, Changsha, 410006, Hunan, China.

Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and miRNA-gene pairs, and Perl software was used to find overlapping genes between DEGs and DEM target genes. There were 129 overlapping genes regulated by nine miRNAs between target genes of the DEMs and DEGs. The Chinese Glioma Genome Atlas(CGGA) was analyzed in order to identify miRNAs with diagnostic and prognostic significance. MiR-139-5p, miR-137, and miR-338-3p were validated to be significantly linked to prognosis in glioma patients. Finally, we validated that miR-139-5p affected glioma malignant biological behavior via targeting gamma-aminobutyric acid A receptor alpha 1(GABRA1) through rescue experiments. Low miR-139-5p expression was correlated with survival probability and World Health Organization (WHO) grade. MiR-139-5p overexpression inhibited cell proliferation, migration, and invasion of glioma in vitro. GABRA1 was identified as a functional downstream target of miR-139-5p. Decreased GABRA1 expression was related to similar biological roles as miR-139-5p overexpression while upregulation of GABRA1 effectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.
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http://dx.doi.org/10.1186/s12967-021-02880-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130534PMC
May 2021

Provincial Greenhouse Gas Emissions of Gasoline and Plug-in Electric Vehicles in China: Comparison from the Consumption-Based Electricity Perspective.

Environ Sci Technol 2021 05 4;55(10):6944-6956. Epub 2021 May 4.

Aramco Services Company, Aramco Research Center-Detroit, Novi, Michigan 48377, United States.

China has implemented strong incentives to promote the market penetration of plug-in electric vehicles (PEVs). In this study, we compare the well-to-wheels (WTW) greenhouse gas (GHG) emission intensities of PEVs with those of gasoline vehicles at the provincial level in the year 2017 by considering the heterogeneity in the consumption-based electricity mix and climate impacts on vehicle fuel economy. Results show a high variation of provincial WTW GHG emission intensities for battery electric vehicles (BEVs, 22-293 g COeq/km) and plug-in hybrid electric vehicles (PHEVs, 82-298 g COeq/km) in contrast to gasoline internal combustion engine vehicles (ICEVs, 227-245 g COeq/km) and gasoline hybrid electric vehicles (HEVs, 141-164 g COeq/km). Due to the GHG-intensive coal-based electricity and cold weather, WTW GHG emission intensities of BEVs and PHEVs are higher than those of gasoline ICEVs in seven and ten northern provinces in China, respectively. WTW GHG emission intensities of gasoline HEVs, on the other hand, are lower in 18 and 26 provinces than those of BEVs and PHEVs, respectively. The analysis suggests that province-specific PEV and electric grid development policies should be considered for GHG emission reductions of on-road transportation in China.
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http://dx.doi.org/10.1021/acs.est.0c08217DOI Listing
May 2021

Active MT1-MMP is tethered to collagen fibers in DDR2-containing remnants.

Gene 2021 Jul 18;788:145673. Epub 2021 Apr 18.

Research Center for High Altitude Medicine, Qinghai University, Xining, Qinghai 810001, China. Electronic address:

Type I collagen is a major extracellular matrix (ECM) component in the interstitial stroma of solid tumors, and it represents the first barrier against tumor cell invasion after basement-membrane degradation. The collagen receptors that convey molecular signals into the cells are collagen-binding discoidin domain receptors (DDRs) and integrins. Collagen-activated DDR2 clusters form DDR2-containing remnants in an integrin-dependent manner in three-dimensional (3D) collagen matrix. Although DDR2-containing remnants in the collagen matrix may generate sustained perturbation to ECM remodeling, the molecular components and function of the remnants are largely unknown. Here we determined the interaction and co-localization between DDR2 and membrane type I-matrix metalloproteinase (MT1-MMP) in the cells and the DDR2-containing remnants on collagen fibers, and we found that MT1-MMP was co-tethered to collagen fibers in the remnants. These collagen fiber-associated MT1-MMP remained active. Furthermore, DDR2 enhanced MT1-MMP proteolytic activity. These results demonstrate that DDR2 ensures the remnant-associated MT1-MMP to continue the degradation of ECM in addition to pericellular ECM degradation mediated by cell surface tethered MT1-MMP. Thus, our findings reveal a new alternative ECM degradation mechanism mediated by MT1-MMP in the DDR2-containing remnants.
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http://dx.doi.org/10.1016/j.gene.2021.145673DOI Listing
July 2021

Multilevel prioritization of gene regulators associated with consensus molecular subtypes of colorectal cancer.

Brief Bioinform 2021 Sep;22(5)

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150086, China.

Consensus molecular subtypes (CMSs) are emerging as critical factor for prognosis and treatment of colorectal cancer. Gene regulators, including chromatin regulator, RNA-binding protein and transcriptional factor, are critical modulators of cancer hallmark, yet little is known regarding the underlying functional mechanism in CMSs. Herein, we identified a core set of 235 functional gene regulators (FGRs) by integrating genome, epigenome, transcriptome and interactome of CMSs. FGRs exhibited significant multi-omics alterations and impacts on cell lines growth, as well as significantly enriched cancer driver genes and pathways. Moreover, common FGRs played different roles in the context of CMSs. In accordance with the immune characteristics of CMSs, we found that the anti-tumor immune pathways were mainly activated by FGRs (e.g. STAT1 and CREBBP) in CMS1, while inhibited by FGRs in CMS2-4. FGRs mediated aberrant expression of ligands, which bind to receptor on immune cells, and modulated tumor immune microenvironment of subtypes. Intriguingly, systematic exploration of datasets using genomic and transcriptome co-similarity reveals the coordinated manner in FGRs act in CMSs to orchestrate their pathways and patients' prognosis. Expression signatures of the FGRs revealed an optimized CMS classifier, which demonstrated 88% concordance with the gold-standard classifier, but avoiding the influence of sample composition. Overall, our integrative analysis identified FGRs to regulate core tumorigenic processes/pathways across CMSs.
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http://dx.doi.org/10.1093/bib/bbab077DOI Listing
September 2021

Cereblon expression is a prognostic marker in newly diagnosed POEMS syndrome treated with lenalidomide plus dexamethasone.

Ann Hematol 2021 Jun 10;100(6):1547-1552. Epub 2021 Apr 10.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

POEMS syndrome is a rare plasma cell disorder. Lenalidomide has recently emerged as a therapeutic option for POEMS syndrome. Cereblon has been identified as the direct target of lenalidomide, and high cereblon expression is associated with better response and outcome to lenalidomide therapy in multiple myeloma patients. Here, we analyzed the predictive value of cereblon, IKZF1, and IKZF3 in CD138 selected plasma cells from forty-one newly diagnosed POEMS syndrome patients treated with lenalidomide in combination with dexamethasone at both gene and protein levels. We found that patients with high cereblon expression tended to achieve better hematologic response compared to those with low expression (p = 0.024 for gene expression; p = 0.01 for protein expression). Multivariate Cox regression analysis revealed high cereblon mRNA expression as an independent prognostic marker for longer progression-free survival (hazard ratio 0.542; 95% CI 0.337-0.871; p = 0.011). In conclusion, our results emphasized the role of cereblon mRNA expression as a unique biomarker for predicting the clinical response and outcome of lenalidomide-based therapy in newly diagnosed POEMS syndrome patients.
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http://dx.doi.org/10.1007/s00277-021-04517-9DOI Listing
June 2021

Identification of differential DNA methylation alterations of ovarian cancer in peripheral whole blood based on within-sample relative methylation orderings.

Epigenetics 2021 Mar 22:1-13. Epub 2021 Mar 22.

School of Medical Information Engineering, Gannan Medical University, Ganzhou, China.

Leukocyte cell proportion changes affect the detection of cancer-associated aberrant DNA methylation alterations in peripheral blood samples. We aimed to detect cellular DNA methylation changes in ovarian cancer (OVC) blood samples avoiding the above-mentioned cell-composition effects. Based on the within-sample relative methylation orderings (RMOs) of CpG loci in leukocyte subtypes, we developed the Ref-RMO method to detect aberrant methylation alterations from OVC blood samples. Stable CpG pairs with consistent RMOs in different leukocyte subtypes were determined, more than 99% of which retained their RMO patterns in peripheral whole blood (PWB) in independent datasets. Based on the stable CpG pairs, significantly reversed CpG pairs were detected from OVC PWB samples, which were relative to clinical information such as age, subtype, grade, stage, or CA125 level. Results showed 439 CpG loci were determined to be significant differential DNA methylations between OVC and healthy blood samples. They were mainly enriched in KEGG pathways, such as cytokine-cytokine receptor interaction, apoptosis, proteoglycans in cancer, and immune-associated Gene Ontology terms. STRING analysis showed that they tended to have functional interactions with cancer-associated genes recorded in the COSMIC database. Leukocyte cellular differential DNA methylations could be identified by the proposed RMO-based method from OVC PWB samples, which were cancer-associated aberrant signals against cell-composition effects.
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http://dx.doi.org/10.1080/15592294.2021.1900029DOI Listing
March 2021

Genetic diversity analysis of Dermacentor nuttalli within Inner Mongolia, China.

Parasit Vectors 2021 Mar 1;14(1):131. Epub 2021 Mar 1.

Inner Mongolia Center for Disease Control and Prevention, Hohhot, 010000, Inner Mongolia, China.

Background: Ticks (Arthropoda, Ixodida), after mosquitoes, are the second most prevalent vector of infectious diseases. They are responsible for spreading a multitude of pathogens and threatening the health and welfare of animals and human beings. However, given the history of tick-borne pathogen infections in the Inner Mongolia Autonomous Region of China, surprisingly, neither the genetic diversity nor the spatial distribution of haplotypes within ticks has been studied.

Methods: We characterized the haplotype distribution of Dermacentor nuttalli in four main pastoral areas of the Inner Mongolia Autonomous Region, by sampling 109 individuals (recovered from sheep) in April-August 2019. The 16S rRNA gene, cytochrome c oxidase subunit I (COI), and the internal transcribed spacer 2 region (ITS2) were amplified and sequenced from extracted DNA.

Results: Twenty-six haplotypes were identified using 16S rRNA sequences, 57 haplotypes were identified with COI sequences, and 75 haplotypes were identified with ITS2 sequences. Among the three genes, total haplotype diversity was greater than 0.7, while total nucleotide diversity was greater than 0.06. Neutrality tests revealed a significantly negative Tajima's D result, while Fu's Fs was not significantly positive. Fixation index values (F) indicated that the degree of genetic differentiation among some sampled populations was small, while for others it was moderate. Analysis of molecular variance (AMOVA) revealed that the variation within populations was greater than that among populations. The mismatch analysis of D. nuttalli exhibited double peaks.

Conclusion: The genetic diversity of D. nuttalli populations in our region can likely adapt to different geographical environments, thereby leading to genetic diversity, and creating genetic differentiation among different populations. However, genetic differentiation is cryptic and does not form a pedigree geographical structure.
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http://dx.doi.org/10.1186/s13071-021-04625-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923491PMC
March 2021

Cathepsin B-responsive and gadolinium-labeled branched glycopolymer-PTX conjugate-derived nanotheranostics for cancer treatment.

Acta Pharm Sin B 2021 Feb 14;11(2):544-559. Epub 2020 Aug 14.

Huaxi MR Research Center (HMRRC), Department of Neurosurgery, and Department of Radiology, Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China.

Multi-modal therapeutics are emerging for simultaneous diagnosis and treatment of cancer. Polymeric carriers are often employed for loading multiple drugs due to their versatility and controlled release of these drugs in response to a tumor specific microenvironment. A theranostic nanomedicine was designed and prepared by complexing a small gadolinium chelate, conjugating a chemotherapeutic drug PTX through a cathepsin B-responsive linker and covalently bonding a fluorescent probe pheophorbide a (Ppa) with a branched glycopolymer. The branched prodrug-based nanosystem was degradable in the tumor microenvironment with overexpressed cathepsin B, and PTX was simultaneously released to exert its therapeutic effect. The theranostic nanomedicine, branched glycopolymer-PTX-DOTA-Gd, had an extended circulation time, enhanced accumulation in tumors, and excellent biocompatibility with significantly reduced gadolinium ion (Gd) retention after 96 h post-injection. Enhanced imaging contrast up to 24 h post-injection and excellent antitumor efficacy with a tumor inhibition rate more than 90% were achieved from glycopolymer-PTX-DOTA-Gd without obvious systematic toxicity. This branched polymeric prodrug-based nanomedicine is very promising for safe and effective diagnosis and treatment of cancer.
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http://dx.doi.org/10.1016/j.apsb.2020.07.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893117PMC
February 2021

β-elemene promotes the senescence of glioma cells through regulating YAP-CDK6 signaling.

Am J Cancer Res 2021 1;11(2):370-388. Epub 2021 Feb 1.

Key Laboratory of β-elemene Anti-cancer Medicine of Zhejiang Province and Holistic Integrative Pharmacy Institutes, and Department of Neurosurgery, The Affiliated Hospital, Hangzhou Normal University Hangzhou 311121, Zhejiang, China.

Glioma is currently the most widespread and malignant primary intracranial tumor, which is characterized by high heterogeneity and high fatality rates. β-elemene, which is a bioactive compound extracted from a Chinese herb, Curcuma wenyujin, has been reported to reduce resistance of chemotherapeutic drugs and induce apoptosis in tumor cells. However, the role and mechanisms of β-elemene in glioma senescence remains unknown. In the present study, we found that a low concentration of β-elemene (10 μg/mL) induced senescence in glioma cells, including reduction of cell proliferation, hypertrophic morphology, increase of senescence-associated β-galactosidase (SA-β-Gal) activity, upregulation of several senescence-associated genes such as and , and downregulation of . However, a high concentration of β-elemene induced apoptosis in glioma cells. Treatment with β-elemene caused a marked down-regulation of Yes-associated protein (YAP) expression in glioma cells, which is a key transcriptional co-activator in multiple cancers. Moreover, cyclin dependent kinase 6 (CDK6), which is a known downstream target of YAP, was decreased in glioma cells that treated with β-elemene. The overexpression of YAP and CDK6 significantly rescued β-elemene-induced senescence in glioma cells. Finally, β-elemene treatment also induced the senescence of glioma cells in glioma xenograft model through inactivation of YAP-CDK6 pathways, which might inhibit the glioma growth. Taken together, these results reveal a previously unknown role of β-elemene in glioma cell senescence and that is associated with YAP-CDK6 signaling pathway, which will enhance our understanding of glioma cell senescence, and provide novel strategies for the treatment of gliomas.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868755PMC
February 2021

Anti-LYPD1/CD3 T-Cell-Dependent Bispecific Antibody for the Treatment of Ovarian Cancer.

Mol Cancer Ther 2021 04 3;20(4):716-725. Epub 2021 Feb 3.

Genentech Inc., South San Francisco, California.

Ovarian cancer is a diverse class of tumors with very few effective treatment options and suboptimal response rates in early clinical studies using immunotherapies. Here we describe LY6/PLAUR domain containing 1 (LYPD1) as a novel target for therapeutic antibodies for the treatment of ovarian cancer. LYPD1 is broadly expressed in both primary and metastatic ovarian cancer with ∼70% prevalence in the serous cancer subset. Bispecific antibodies targeting CD3 on T cells and a tumor antigen on cancer cells have demonstrated significant clinical activity in hematologic cancers. We have developed an anti-LYPD1/CD3 T-cell-dependent bispecific antibody (TDB) to redirect T-cell responses to LYPD1 expressing ovarian cancer. Here we characterize the nonclinical pharmacology of anti-LYPD1/CD3 TDB and show induction of a robust polyclonal T-cell activation and target dependent killing of LYPD1 expressing ovarian cancer cells resulting in efficient antitumor responses in PBMC reconstituted immune-deficient mice and human CD3 transgenic mouse models. Anti-LYPD1/CD3 TDB is generally well tolerated at high-dose levels in mice, a pharmacologically relevant species, and showed no evidence of toxicity or damage to LYPD1 expressing tissues.
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http://dx.doi.org/10.1158/1535-7163.MCT-20-0490DOI Listing
April 2021

Enhancing the Therapeutic Efficacy of Gefitinib in Human Non-Small-Cell Lung Cancer through Drug Combination.

Mol Pharm 2021 03 20;18(3):1397-1407. Epub 2021 Jan 20.

Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Tiantanxili, Beijing 100050, China.

The interaction between tumor cells and the tumor microenvironment (TME) significantly influences tumorigenesis, so TME-targeted therapy has attracted widespread attention. We have previously demonstrated that the combination of dipyridamole, bestatin, and dexamethasone (DBD mix, DBDx) is effective against heterogeneous human pancreatic cancer and hepatocellular carcinoma in mouse xenograft models. To further expand the therapeutic potential of this drug combination, herein, we investigated the antitumor efficacy and the underlying mechanism of DBDx and the combination of DBDx and gefitinib in different mouse xenograft models of human non-small-cell lung cancer (NSCLC). Three human cancer cell lines H460, PG, and A431 were used to determine the apoptosis and growth inhibition induced by DBDx, gefitinib, and their combinations. Changes in epidermal growth factor receptor (EGFR) signaling pathway-related proteins were analyzed following treatment using western blotting. , DBDx strongly inhibited the proliferation of tumor cells, whereas the combined treatment exhibited a significant synergistic effect. Compared with DBDx, the combination treatment further induced apoptosis and downregulated the expression of molecules associated with EGFR signaling pathway. , compared with DBDx alone, the combination treatment distinctly inhibited tumor growth in mouse xenograft models of human NSCLC. Overall, our results indicate that the combination of DBDx and gefitinib in the treatment of human NSCLC is very promising, which warrants further translational studies.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01203DOI Listing
March 2021

Hypoxia-inducible factor-2 promotes liver fibrosis in non-alcoholic steatohepatitis liver disease via the NF-κB signalling pathway.

Biochem Biophys Res Commun 2021 02 12;540:67-74. Epub 2021 Jan 12.

Research Center for High Altitude Medicine, Qinghai University Medical College, Xining, 810001, China; Key Laboratory of High Altitude Medicine(Qinghai University), Ministry of Education, Xining, 810001, China; Key Laboratory for Application of High Altitude Medicine in Qinghai Province, Xining, 810001, PR China. Electronic address:

Non-alcoholic steatohepatitis (NASH) is one of the most common chronic liver diseases. Chronic hypoxia is related to the pathogenesis of NASH. HIF-2α is the key gene for lipid metabolism, fibrosis, and inflammation in many cells. To identify the molecular mechanism through which hypoxia exposure increases the morbidity of NASH, the expression level of HIF-2α was analysed and was found to be upregulated in human NASH liver. By constructing the NASH model of chronic hypoxia, the mice were housed at an altitude of 4300 m for 4 and 8 weeks, compared to the control groups that were housed at an altitude of 50 m. Histological studies showed that exposure to hypoxia promoted the activation of NF-κB by upregulating the expression of HIF-2α, as well as that of the genes related to inflammation and fibrosis, thereby promoting the development of NASH both in vivo and in vitro. In summary, hypoxia-exposure could upregulate HIF-2α to aggravate tissue fibrosis and inflammation by upregulating inflammation-related genes and fibrosis-related genes metabolites via the activated NF-κB pathway in NASH. Our results suggest that for NASH patients living at high altitudes, drug therapy could focus on treating tissue fibrosis and inflammation, and thus provides a new strategy for NASH treatment.
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http://dx.doi.org/10.1016/j.bbrc.2021.01.002DOI Listing
February 2021

IL‑6 plays a crucial role in epithelial‑mesenchymal transition and pro‑metastasis induced by sorafenib in liver cancer.

Oncol Rep 2021 03 7;45(3):1105-1117. Epub 2021 Jan 7.

Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, P.R. China.

Interleukin‑6 (IL‑6) is involved in various biological responses, including tumor progression, metastasis and chemoresistance. However, the role and molecular mechanism of IL‑6 in the treatment of sorafenib in liver cancer remain unclear. In the present study, through western blot analysis, Transwell assay, flow cytometric assay, ELISA analysis and immunohistochemistry it was revealed that sorafenib promoted metastasis and induced epithelial‑mesenchymal transition (EMT) in liver cancer cells in vitro and in vivo, and significantly increased IL‑6 expression. Endogenous or exogenous IL‑6 affected metastasis and EMT progression in liver cancer cells through Janus kinase 2/signal transducer and activator of transcription 3 (STAT3) signaling. Knocked out IL‑6 markedly attenuated the pro‑metastasis effect of sorafenib and increased the susceptibility of liver cancer cells to it. In conclusion, the present results indicated that IL‑6/STAT3 signaling may be a novel therapeutic strategy for liver cancer.
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http://dx.doi.org/10.3892/or.2021.7926DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859995PMC
March 2021

A case report on concurrent occurrence of systemic mastocytosis and myeloid sarcoma presenting with extensive skin involvements and the results of genetic study.

Medicine (Baltimore) 2020 Dec;99(50):e21948

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Introduction: Systemic mastocytosis is a rare disease due to mast cell accumulation in various extracutaneous sites. Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease is the second most common subtype of systemic mastocytosis. The most common mutation associated with both systemic mastocytosis and myeloid sarcoma is mutation in Kit. Here, we identified the novel KIT D816V and ARID1A G1254S mutations co-occurring in systemic mastocytosis with myeloid sarcoma.

Patient Concerns: A 33-year old male patient presented multiple skin lesions for 10 years. Symptoms accelerated in 2017 with decreased body weight. Physical examination revealed enlarged lymph nodes in his neck, axilla and inguinal region; conjunctival hemorrhage; gingival hyperplasia. Skin biopsy showed mast cell infiltration. Flow cytometry detected CD2, CD25 and CD117 positive cells in lymph nodes. Codon 816 KIT mutation D816V and codon 1245 ARID1A mutation G1254S were found in peripheral blood. MPO, CD117, CD68 positive cells in lymph nodes indicated co-existing myeloid sarcoma.

Diagnosis: Systemic mastocytosis with an associated clonal hematologic non-MC lineage disease of myeloid sarcoma INTERVENTIONS:: Cytarabine and daunorubicin for myeloid sarcoma and dasatinib for systemic mastocytosis were initiated. Anti-histamine and anti-leukotrienes therapy were used to prevent NSAIDs-induced shock. Platelets were infused to treat bone marrow suppression.

Outcomes: Patient was discharged after recovered from bone marrow suppression. Dasatinib continued on outpatient.

Conclusion: This is the first case of patient with systemic mastocytosis and myeloid sarcoma simultaneously presenting extensive skin involvements. Mutations of Kit and Arid1a emphasis the importance to notice possibility of various tumors occurring in patients with multiple mutations. In addition, cysteine-leukotrienes-receptor antagonists should always be used to prevent anaphylactic shock due to mast cell activation.
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http://dx.doi.org/10.1097/MD.0000000000021948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738061PMC
December 2020

Dynamic folding modulation generates FGF21 variant against diabetes.

EMBO Rep 2021 01 9;22(1):e51352. Epub 2020 Dec 9.

High Magnetic Field Laboratory, CAS Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

Fibroblast growth factor 21 (FGF21) is a regulator of glucose and lipid metabolism. It has been widely considered as a promising candidate for the treatment of type 2 diabetes mellitus (T2DM) and other related metabolic disorders. However, lack of structural and dynamic information has limited FGF21-based drug development. Here, using nuclear magnetic resonance (NMR) spectroscopy, we determine the structure of FGF21 and find that its non-canonical flexible β-trefoil conformation affects the folding of β2-β3 hairpin and further overall protein stability. To modulate folding dynamics, we designed an FGF21-FGF19 chimera, FGF21 . As expected, FGF21 shows better thermostability without inducing hepatocyte proliferation. Functional characterization of FGF21 shows its better insulin sensitivity, reduced inflammation in 3T3-L1 adipocytes, and lower blood glucose and insulin levels in ob/ob mice compared with wild type. Our dynamics-based rational design provides a promising approach for FGF21-based therapeutic development against T2DM.
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http://dx.doi.org/10.15252/embr.202051352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788455PMC
January 2021

A highly heterogeneous mutational pattern in POEMS syndrome.

Leukemia 2021 04 1;35(4):1100-1107. Epub 2020 Dec 1.

Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, 100730, Beijing, China.

POEMS syndrome is a rare plasma cell dyscrasia. Little is known about its pathogenesis and genetic features. We analyzed the mutational features of purified bone marrow plasma cells from 42 patients newly diagnosed with POEMS syndrome using a two-step strategy. Whole exome sequencing of ten patients showed a total of 170 somatic mutations in exonic regions and splicing sites, with paired peripheral blood mononuclear cells as a control. Three significantly mutated genes-LILRB1 (10%), HEATR9 (20%), and FMNL2 (10%)-and eight mutated known driver genes (MYD88, NFKB2, CHD4, SH2B3, POLE, STAT3, CHD3, and CUX1) were identified. Target region sequencing of 77 genes were then analyzed to validate the mutations in an additional 32 patients. A total of 32 mutated genes were identified, and genes recurrently mutated in more than three patients included CUX1 (19%), DNAH5 (16%), USH2A (16%), KMT2D (16%), and RYR1 (12%). Driver genes of multiple myeloma (BIRC3, LRP1B, KDM6A, and ATM) and eleven genes reported in light-chain amyloidosis were also identified in target region sequencing. Notably, VEGFA mutations were detected in one patient. Our study revealed heterogeneous genomic profiles of bone marrow plasma cells in POEMS syndrome, which might share some similarity to that of other plasma cell diseases.
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http://dx.doi.org/10.1038/s41375-020-01101-4DOI Listing
April 2021

A Five-Gene-Pair-Based Prognostic Signature for Predicting the Relapse Risk of Early Stage ER+ Breast Cancer.

Front Genet 2020 29;11:566928. Epub 2020 Oct 29.

Department of Bioinformatics, Fujian Key Laboratory of Medical Bioinformatics, Key Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.

About 20-30% of early-stage breast cancer patients suffer relapses after surgery. To identify such high-risk patients, many signatures have been reported, but they lack robustness in data measured on different platforms. Here, we developed a signature which is robust across multiple profiling platforms, and identified reproducible omics features characterizing metastasis of estrogen receptor (ER)-positive breast cancer from the Gene Expression Omnibus database with the aid of the signature. Based on the stable within-sample relative expression orderings (REOs), we constructed a signature consisting of five gene pairs, named 5-GPS, whose REOs were significantly correlated with relapse-free survival using the univariate Cox regression model. Using 5-GPS, patients were classified into the low-risk and high-risk groups. Patients in the high-risk group have worse survival compared to those in the low-risk group using Kaplan-Meier curve analysis with the log-rank test. Applying 5-GPS to the RNA-sequencing data of stage I-IV breast cancer samples archived in The Cancer Genome Atlas (TCGA), we found that the proportion of the high-risk patients increases with the stage. The proposed REO-based signature shows potential in identifying early-stage ER+ breast cancer patients with high risk of relapse after surgery.
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http://dx.doi.org/10.3389/fgene.2020.566928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658391PMC
October 2020

Do the existing staging systems for primary liver cancer apply to combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma?

Hepatobiliary Pancreat Dis Int 2021 Feb 27;20(1):13-20. Epub 2020 Oct 27.

Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai 200032, China. Electronic address:

Background: The incidence of combined hepatocellular carcinoma-intrahepatic cholangiocarcinoma (cHCC-ICC) is relatively low, and the knowledge about the prognosis of cHCC-ICC remains obscure. In the study, we aimed to screen existing primary liver cancer staging systems and shed light on the prognosis and risk factors for cHCC-ICC.

Methods: We retrospectively reviewed 206 cHCC-ICC patients who received curative surgical resection from April 1999 to March 2017. The correlation of survival measures with the histological types or with tumor staging systems was determined and predictive values of tumor staging systems with cHCC-ICC prognosis were compared.

Results: The histological type was not associated with overall survival (OS) (P = 0.338) or disease-free survival (DFS) (P = 0.843) of patients after curative surgical resection. BCLC, TNM for HCC, and TNM for ICC stages correlated with both OS and DFS in cHCC-ICC (all P < 0.05). The predictive values of TNM for HCC and TNM for ICC stages were similar in terms of predicting postoperative OS (P = 0.798) and DFS (P = 0.191) in cHCC-ICC. TNM for HCC was superior to BCLC for predicting postoperative OS (P = 0.022) in cHCC-ICC.

Conclusion: The TNM for HCC staging system should be prioritized for clinical applications in predicting cHCC-ICC prognosis.
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http://dx.doi.org/10.1016/j.hbpd.2020.10.002DOI Listing
February 2021
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