苏旭;史维俊;王静;吴华彰;

• 1:蚌埠医学院生命科学学院癌症转化医学安徽省重点实验室
• 2:蚌埠医学院第一附属医院胃肠外科

摘要(Abstract)：

目的应用生物信息学方法分析筛选胃癌患者差异表达基因,探讨其在胃癌发生发展及预后中的临床价值及意义。方法在癌症基因组图谱(The cancer Genome Atlas, TCGA)数据库中下载胃癌基因表达相关的数据,利用Perl构建基因表达矩阵并提取患者临床病理信息;利用R语言中的edgeR程序包筛选表达差异基因;UALCAN在线网站进行基因差异表达、临床病理信息及生存分析。采用Cox回归及Kaplan-Meier Plotter在线分析目的基因与胃癌患者预后的相关性。最后,利用基因集富集分析(gene-set enrichment analysis, GSEA)对靶基因进行KEGG(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析,探讨其参与胃癌发生发展的信号通路及可能分子机制。结果通过对TCGA数据库的数据分析获得2676个差异化表达基因;UALCAN在线网站分析差异化基因,显示PDGFRB基因在胃癌组织中显著高表达,且与胃癌患者的临床病理及不良预后显著相关(P<0.01);生存分析提示PDGFRB基因高表达时,胃癌患者的预后相对较差;STRING在线网站和GSEA软件分析表明,PDGFRB基因可能通过调控Wnt信号通路来影响胃癌的发生发展。结论 PDGFRB基因可作为胃癌独立的预后基因,可能通过调控Wnt信号通路影响胃癌的发生发展,并有望成为治疗胃癌的新的诊断标记和潜在治疗靶标。

关键词(KeyWords)： 胃癌;生物信息学分析;PDGFRB;预后;Wnt信号通路

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(21707002);; 安徽省自然科学基金(1908085MH257);; 蚌埠医学院转化医学重点专项(BYTM2019008)

作者(Authors): 苏旭;史维俊;王静;吴华彰;

DOI: 10.13799/j.cnki.mdjyxyxb.2021.03.010

参考文献(References)：

• [1] BRAY F,FERLAY J,SOERJOMATARAM I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
• [2] TARAZONA N,GAMBARDELLA V,HUERTA M,et al.Personalised Treatment in Gastric Cancer:Myth or Reality?[J].Curr Oncol Rep,2016,18(7):41.
• [3] NAMIKAWA T,ISHIDA N,YOKOTA K,et al.Multidisciplinary Treatment for a Patient with Recurrent Gastric Cancer,Presenting 13 Years after the Radical Gastrectomy[J].Gan To Kagaku Ryoho,2019(46):2087-2089.
• [4] MARKHAM M J,WACHTER K,AGARWAL N,et al.Clinical Cancer Advances 2020:Annual Report on Progress Against Cancer From the American Society of Clinical Oncology[J].J Clin Oncol,2020,38(10):1081.
• [5] VAN CUTSEM E,SAGAERT X,TOPAL B,et al.Gastric cancer[J].Lancet,2016(12):2654-2664.
• [6] ZHANG H,DENG T,LIU R,et al.Exosome-delivered EGFR regulates liver microenviroment to promote gastric cancer live metastasis[J].Nat Commun,2017(4):15016.
• [7] ZHIHONG Z,RUBIN C,LIPING L,et al.MicroRNA-1179 regulates proliferation and chemosensitivity of human ovarian cancer cells by targeting the PTEN-mediated PI3K/AKT signaling pathway[J].Arch Med Sci,2020(16):907-914.
• [8] LAKOMY D S,URBAUER D L,WESTIN S N,et al.Phase I study of the PARP inhibitor talazoparib with radiation therapy for locally recurrent gynecologic cancers[J].Clin Transl Radiat Oncol,2020(21):56-61.
• [9] DENG M,BRAGELMANN J,SCHULTZE J L,et al.Web-tcga:An online platform for integrated analysis of molecular cancer data sets[J].BMC Bioinformatics,2016(17):72.
• [10] WANG Y,SONG B,ZHU L,et al.Long non-coding RNA,LINC01614 as a potential biomarker for prognostic prediction in breast cancer[J].Peer J,2019(7):7976.
• [11] FEJES A V,BEST M G,VANCURA A,et al.Impact of Escherichia coli K12 and O18:K1 on human platelets:Differential effects on platelet activation,RNAs and proteins[J].Sci Rep,2018,8(1):16145.
• [12] REIMAND J,ISSERLIN R,VOISIN V,et al.Pathway enrichment analysis and visualization of omics data using g:Profiler,gsea,cytoscape and enrichmentmap[J].Nat Protoc,2019(14):482-517.
• [13] RITCHIE M E,PHIPSON B,WU D,et al.limma powers differential expression analyses for RNA-sequencing and microarray studies[J].Nucleic Acids Res,2015,43(7):47.
• [14] BO Y,FENG J,XU J,et al.High-resolution pure shift NMR spectroscopy offers better metabolite discrimination in food quality analysis[J].Food Res Int,2019(125):108574.
• [15] ARNOLD M,PARK J Y,CAMARGO M C,et al.Soerjomataram I.Is gastric cancer becoming a rare disease?A global assessment of predicted incidence trends to 2035[J].Gut,2020,69(5):823-829.
• [16] MA D,MENG F D.Diagnosis and treatment of Helicobacter pylori infection and early gastric cancer[J].Zhong Hua Nei Ke Za Zhi,2020(59):392-394.
• [17] LI H,LIU J W,LIU S,et al.Bioinformatics-Based Identification of Methylated-Differentially Expressed Genes and Related Pathways in Gastric Cancer[J].Dig Dis Sci,2017(62):3029-3039.
• [18] LI S,LIU F,XU L,et al.Wnt/beta-catenin signaling axis is required for TFEB-mediated gastric cancer metastasis and epithelial-mesenchymal transition[J].Mol Cancer Res,2020,18(11):1650-1659.
• [19] WANG X,WANG X,LIU Y,et al.LGR5 regulates gastric adenocarcinoma cell proliferation and invasion via activating Wnt signaling pathway[J].Oncogenesis,2018,7(8):57.
• [20] YONG X,TANG B,XIAO Y F,et al.Helicobacter pylori upregulates Nanog and Oct4 via Wnt/β-catenin signaling pathway to promote cancer stem cell-like properties in human gastric cancer[J].Cancer Lett,2016,374(2):292-303.
• [21] ZHANG Z,WANG J,DONG X.Wnt2 contributes to the progression of gastric cancer by promoting cell migration and invasion[J].Oncol Lett,2018,16(3):2857-2864.
• [22] ZHANG H,XIE T,SHUI Y,et al.Knockdown of PLCB2 expression reduces melanoma cell viability and promotes melanoma cell apoptosis by altering Ras/Raf/MAPK signals[J].Mol Med Rep,2020,21(1):420-428.
• [23] YANG S,LIU Y,LI M Y,et al.FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer[J].Mol Cancer,2017(16):124.
• [24] RUSSELL J O,MONGA S P.Wnt/β-Catenin Signaling in Liver Development,Homeostasis,and Pathobiology[J].Annu Rev Pathol,2018(13):351-378.
• [25] FENG Z Y,XU X H,CEN D Z,et al.miR-590-3p promotes colon cancer cell proliferation via Wnt/β-catenin signaling pathway by inhibiting WIF1 and DKK1[J].Eur Rev Med Pharmacol Sci,2017(21):4844-4852.
• [26] REDDY D,GHOSH P,KUMAVATH R.Strophanthidin Attenuates MAPK,PI3K/AKT/mTOR,and Wnt/beta-Catenin Signaling Pathways in Human Cancers[J].Front Oncol,2019(9):1469.
• [27] LI H,HE X,PENG Y,et al.Erratum:LOXL1 regulates cell apoptosis and migration in human neuroglioma U87 and U251 cells via Wnt/beta-catenin signaling[J].Int J Clin Exp Pathol,2019(12):3164.
• [28] LIN K,LIU B,LIM S L,et al.20(S)-protopanaxadiol promotes the migration,proliferation,and differentiation of neural stem cells by targeting GSK-3beta in the Wnt/GSK-3beta/beta-catenin pathway[J].J Ginseng Res,2020(44):475-482.
• [29] ZHANG Z,ZHANG Y,QIN X et al.FGF9 promotes cisplatin resistance in colorectal cancer via regulation of Wnt/beta-catenin signaling pathway[J].Exp Ther Med,2020(19):1711-1718.
• [30] ZHENG L,ZHENG Q,YU Z,et al.Liuwei Dihuang pill suppresses metastasis by regulating the wnt pathway and disrupting-catenin/T cell factor interactions in a murine model of triple-negative breast cancer[J].J Tradit Chin Med,2019(39):826-832.