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ISSN Печать: 1045-4403
ISSN Онлайн: 2162-6502
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Identification of Hub Genes in Gastric Cancer with High Heterogeneity Based on Weighted Gene Co-Expression Network
Краткое описание
Intra-tumor heterogeneity (ITH) plays an important role in the therapeutic resistance and prognosis of gastric cancer (GC), but there are no effective methods to detect it. The purpose of this study was to apply the mutant-allele tumor heterogeneity (MATH) algorithm to reveal the relationship between ITH and clinical features, and to use weighted gene co-expression network analysis (WGCNA) to search hub genes. The whole exome sequencing data with tumor mutations, RNA-seq, and clinical data were obtained from The Cancer Genome Atlas database. We calculated the MATH values and further investigated their relationships with clinical features and key genes screened out from molecular classification published by Nature. The WGCNA method was applied to discover hub genes within the high ITH cases. We found that MATH values were related to grade classification (P < 0.05). Our study also showed a "high MATH" group with a higher TP53 percentage (P < 0.001), whereas PIK3CA and RHOA had the opposite results (P = 0.004; P = 0.031). Using WGCNA, we found that red module, black module, and brown module were enriched in spliceosome, ribosome, and butanoate metabolism, and their hub genes were PSMD1, RPS23, and FAM84B, respectively. Together, these results demonstrate that in the high MATH group, represented as high heterogeneity, there was a higher frequency of TP53 mutation, and RHOA and PIK3CA tended to appear in the low heterogeneity group. PSMD1, RPS23, and FAM84B were the hub genes in high heterogeneity GC. They were related to the pathology and prognosis of patients.
-
Siegel R, Miller KD, Ahmedin J. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30.
-
Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet. 2016;388(10060):2654-64.
-
Almendro V, Marusyk A, Polyak K. Cellular heterogeneity and molecular evolution in cancer. Annu Rev Pathol. 2013;8(1):277-302.
-
McGranahan N, Swanton C. Clonal heterogeneity and tumor evolution: past, present, and the future. Cell. 2017;168(4):613-28.
-
Ma D, Jiang YZ, Liu XY, Liu YR, Shao ZM. Clinical and molecular relevance of mutant-allele tumor heterogeneity in breast cancer. Breast Cancer Res Treat. 2017;162(1):39-48.
-
Greaves M. Evolutionary determinants of cancer. Cancer Discov. 2015;5(8):806-20.
-
Andor N, Graham TA, Jansen M, Xia LC, Aktipis CA, Petritsch C, Ji HP, Maley CC. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nat Med. 2016 Jan;22(1):105-13.
-
Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J, Cook K, Stepansky A, Levy D, Esposito D, Muthuswamy L, Krasnitz A, McCombie WR, Hicks J, Wigler M. Tumour evolution inferred by single-cell sequencing. Nature. 2011 Apr;472(7341):90-4.
-
Pon JR, Marra MA. Driver and passenger mutations in cancer. Annu Rev Pathol. 2015;10(1):25-50.
-
Vignot S, Frampton GM, Soria JC, Yelensky R, Commo F, Brambilla C, Palmer G, Moro-Sibilot D, Ross JS, Cronin MT, Andre F, Stephens PJ, Lazar V, Miller VA, Brambilla E. Next-generation sequencing reveals high concordance of recurrent somatic alterations between primary tumor and metastases from patients with non-small-cell lung cancer. J Clin Oncol. 2013 Jun 10;31(17):2167-72.
-
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014 Sep;513(7517):202-9.
-
Mroz EA, Rocco JW. MATH, a novel measure of intra- tumor genetic heterogeneity, is high in poor-outcome classes of head and neck squamous cell carcinoma. Oral Oncol. 2013;49(3):211-5.
-
Mroz EA, Tward AD, Pickering CR, Myers J, Ferris RL, Rocco JW. High intratumor genetic heterogeneity is related to worse outcome in head and neck squamous cell carcinoma. Cancer. 2013;119(16):3034-42.
-
Mroz EA, Tward AM, Hammon RJ, Ren Y, Rocco JW. In- tra-tumor genetic heterogeneity and mortality in head and neck cancer: analysis of data from the Cancer Genome Atlas. PLoS Med. 2015;12(2):e1001786.
-
Luo Y, Coskun V, Liang A, Yu J, Cheng L, Ge W, Shi Z, Zhang K, Li C, Cui Y, Lin H, Luo D, Wang J, Lin C, Dai Z, Zhu H, Zhang J, Lie J, Liu H, deVellis J, Horvath S, Sun YE, Li S. Single-cell transcriptome analyses reveal signals to activate dormant neural stem cells. Cell. 2015 May 21;161(5):1175-86.
-
Liu Q, Jiang C, Xu J, Zhao MT, Van Bortle K, Cheng X, Wang G, Chang HY, Wu JC, Snyder MP. Genome-wide temporal profiling of transcriptome and open chromatin of early cardiomyocyte differentiation derived from hiPSCs and hESCs. Circ Res. 2017 Aug 4;121(4):376-91.
-
Spiers H, Hannon E, Schalkwyk LC, Smith R, Wong CC, O'Donovan MC, Bray NJ, Mill J. Methylomic trajectories across human fetal brain development. Genome Res. 2015 Mar 1;25(3):338-52.
-
Spinelli L, Gambette P, Chapple CE, Robisson B, Baudot A, Garreta H, Tichit L, Guenoche A, Bran C. Clust&See: a Cytoscape plugin for the identification, visualization and manipulation of network clusters. Biosystems. 2013 Aug 1;113(2):91-5.
-
Montojo J, Zuberi K, Rodriguez H, Kazi F, Wright G, Donaldson SL, Morris Q, Bader GD. GeneMANIA Cytos-cape plugin: fast gene function predictions on the desktop. Bioinformatics. 2010 Nov 15;26(22):2927-8.
-
Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Syst Biol. 2014;8(Suppl 4):S11.
-
Tan P, Yeoh KG. Genetics and molecular pathogenesis of gastric adenocarcinoma. Gastroenterology. 2015;149(5): 1153-62.
-
Macheret M, Halazonetis TD. DNA replication stress as a hallmark of cancer. Annu Rev Pathol. 2015;10(1):425-48.
-
Soussi T, Wiman KG. Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell. 2007;12(4):303-12.
-
Shimokawa H, Sunamura S, Satoh K. RhoA/Rho-kinase in the cardiovascular system. Circ Res. 2016;118(2):352-66.
-
Ryu1 H, Gygi SP, Azuma Y, Arnaoutov1 A, Dasso M. SU-MOylation of Psmd1 controls Adrm1 interaction with the proteasome. Cell Rep. 2014;7(6):1842-8.
-
Wang Y, Huang JW, Castella M, Huntsman DG, Taniguchi T. p53 is positively regulated by miR-542-3p. Cancer Res. 2014;74(12):3218-27.
-
Wang Shuang, Tian Jun, Wang Jianzhong, Liu Sizhu, Ke Lianwei, Shang Chaojiang, Yang Jichun, Wang Lin, Identification of the Biomarkers and Pathological Process of Heterotopic Ossification: Weighted Gene Co-Expression Network Analysis, Frontiers in Endocrinology, 11, 2020. Crossref
-
Liu Lihua, Liu Aihua, Dong Jun, Zuo Zhongfu, Liu Xuezheng, Proteasome 26S subunit, non-ATPase 1 (PSMD1) facilitated the progression of lung adenocarcinoma by the de-ubiquitination and stability of PTEN-induced kinase 1 (PINK1), Experimental Cell Research, 413, 2, 2022. Crossref
-
Yang Yan, Dai Daofeng, Jin Wen, Huang Yingying, Zhang Yingzi, Chen Yiran, Wang Wankun, Lin Wu, Chen Xiangliu, Zhang Jing, Wang Haohao, Zhang Haibin, Teng Lisong, Microbiota and metabolites alterations in proximal and distal gastric cancer patients, Journal of Translational Medicine, 20, 1, 2022. Crossref