乳头状肾细胞癌差异表达基因和通路生物信息学分析
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摘要
目的探讨生物信息学分析对乳头状肾细胞癌(PRCC)差异表达基因和通路的意义。方法分析癌症基因组图谱(TCGA)数据库中PRCC的RNA测序数据,应用生物信息学分析筛选差异表达基因,并对候选基因依据功能和信号通路进行富集分析。结果分析TCGA中PRCC和癌旁正常组织的RNA测序数据,筛选4 639个差异表达的基因。对筛选差异表达基因进行基因本体及代谢通路富集分析后得到818个基因本体术语(GO terms)和110条信号通路术语(pathway terms)。结论运用edgeR包以及基因本体及信号通路分析,筛选了PRCC与癌旁正常组织差异表达基因及富集的信号通路。
Objective To explore the significance of bioinformatics in the analysis of differentially expressed genes and pathways in papillary renal cell carcinoma(PRCC). Methods The RNA sequencing data of PRCC in the Cancer Genome Atlas database(TCGA) were analyzed. Differentially expressed genes were identified by bioinformatics analysis, and candidate genes were then enriched according to their functions and the signaling pathways in which they were involved. Results RNA sequencing data of PRCC and adjacent normal tissues in TCGA were analyzed and 4639 differentially expressed genes were screened out. After enrichment analyses of gene ontology and metabolic pathways for these differentially expressed genes,818 gene ontology terms and 110 pathway terms were obtained. Conclusion Using the edgeR package and gene ontology and pathway analyses, the differentially expressed genes and enriched signaling pathways between PRCC and adjacent normal tissues were screened out.
Objective To explore the significance of bioinformatics in the analysis of differentially expressed genes and pathways in papillary renal cell carcinoma(PRCC). Methods The RNA sequencing data of PRCC in the Cancer Genome Atlas database(TCGA) were analyzed. Differentially expressed genes were identified by bioinformatics analysis, and candidate genes were then enriched according to their functions and the signaling pathways in which they were involved. Results RNA sequencing data of PRCC and adjacent normal tissues in TCGA were analyzed and 4639 differentially expressed genes were screened out. After enrichment analyses of gene ontology and metabolic pathways for these differentially expressed genes,818 gene ontology terms and 110 pathway terms were obtained. Conclusion Using the edgeR package and gene ontology and pathway analyses, the differentially expressed genes and enriched signaling pathways between PRCC and adjacent normal tissues were screened out.
引文
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[2] SIEGEL R L,MILLER K D.Cancer statistics,2019[J].CA-Cancer J Clin,2019,96(1):7-34.
[3] LJUNGBERG B,CAMPBELL S C,CHO H Y,et al.The epidemiology of renal cell carcinoma[J].European Urology,2011,60(4):615-621.
[4] KING S C,POLLACK L A,LI J,et al.Continued increase in incidence of renal cell carcinoma,especially in young patients and high grade disease:United States 2001 to 2010[J].J Urol,2014,191(6):1665-1670.
[5] SHUCH B,HAHN A W,AGARWAL N.Current treatment landscape of advanced papillary renal cancer[J].J Clin Oncol,2017,35(26):2981-2983.
[6] CONNOR W J,DONSkOV F,FRACCON A P,et al.Cha-racterizing the outcomes of metastatic papillary renal cell carcinoma[J].Cancer Medicine,2017,6(5):902-909.
[7] ALGABA F,AKAZA H,LOPEZ-BELTRAN A,et al.Current pathology keys of renal cell carcinoma[J].Eur Urol,2011,60(4) :634-643.
[8] KLATTE T,PANTUCK A J,SAID J W,et al.Cytogenetic and molecular tumor profiling for type 1 and type 2 papillary renal cell carcinoma[J].Clin Cancer Res,2009,15(4):1162-1169.
[9] LINEHAN W M,SPELLMAN P T,RICKETTS C J,et al.Comprehensive molecular characterization of papillary renal-cell carcinoma[J].N Engl J Med,2016,374(2) :135-145.
[10] OU C,LIU L,WANG J,et al.Enhancement of Siglec-8 expression predicts adverse prognosis in patients with clear cell renal cell carcinoma [J].Urol Oncol,2017,35(10):607-607.
[11] KING R J,YU F,SINGH P K.Genomic alterations in mucins across cancers[J].Oncotarget,2017,8(40):67152-67168.
[12] ALBIGES L,GUEGAN J,FORMAL A L,et al.MET is a potential target across all papillary renal cell carcinomas:result from a large molecular study of pRCC with CGH array and matching gene expression array[J].Clin Cancer Res,2014,20(13):3411-3421.
[13] LIU K,REN Y,PANG L,et al.Papillary renal cell carcinoma:a clinicopathological and whole-genome exon sequencing study[J].Int J Clin Exp Pathol,2015,8(7):8311-8335.
[14] KOVAC M,NAVAS C,HORSWELL S,et al.Recurrent chromosomal gains and heterogeneous driver mutations cha-racterise papillary renal cancer evolution[J].Nat Commun,2015,6(1):6336.
[15] DURINCK S,STAWISKI E W,PAVIA-JIMENEZ A,et al.Spectrum of diverse genomic alterations define non-clear cell renal carcinoma subtypes[J].Nat Genet,2015,47(1):13-21.
[16] ZIMPFER A,MARUSCHKE M,REHN S,et al.Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule(EpCAM)expression in renal tumours:a retrospective clinicopathological study of 948 cases using tissue microarrays[J].BJU Int,2014,114(2):296-302.
[17] BRENNER W,HABER T,JUNKER K,et al.Bone metastasis by renal cell carcinoma.Importance of Calcium and calcium-sensing receptor[J].Urologe A,2015,54(6):839-843.
[18] FREES S,BREUKSCH I,HABER T,et al.Calcium-sensing receptor(CaSR)promotes development of bone metastasis in renal cell carcinoma[J].Oncotarget,2018,9(21):15766-15779.
[19] KORNILUK A,KOPER O,KEMONA H,et al.From inflammation to cancer[J].Ir J Med Sci,2017,186(1):57-62.
[20] BUSSE A,ASEMISSEN A,NONNENMACHER A,et al.Systemic immune tuning in renal cell carcinoma:favorable prognostic impact of TGF-beta1 mRNA expression in perip-heral blood mononuclear cells[J].J Immunother,2011,34(1):113-119.
[21] BINNEWIES M,ROBERTS E W,KERSTEN K,et al.Understanding the tumor immune microenvironment (TIME) for effective therapy[J].Nature Medicine,2018,24(5):541-550.
[22] SULLIVAN L B,GUI D Y,VANDERHEIDEN M G.Altered metabolite levels in cancer:implications for tumour biology and cancer therapy[J].Nat Rev Cancer,2016,16(11):680-693.
[23] OOI A,WONG J C,PETILLO D,et al.An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma[J].Cancer Cell,Oct 18,2011,20(4):511-523.
[24] SRINIVASAN R,RICKETTS C J,SOURBIER C,et al.New strategies in renal cell carcinoma:targeting the genetic and metabolic basis of disease[J].Clin Cancer Res,2015,21(1):10-17.
[25] MARGULIS V,LIN J,YANG H,et al.Genetic susceptibility to renal cell carcinoma:the role of DNA double-strand break repair pathway[J].Cancer Epidemiol Biomarkers Prev,2008,17(9):2366-2373.
[26] DIETLEIN F,THELEN L,REINHARDT H C.Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches [J].Trends Genet,2014,30(8),326-339.
[27] LIN J,PU X,WANG W,et al.Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma[J].Carcinogenesis,2008,29(11):2112-2119.
[28] SAKANO S,HINODA Y,OKAYAMA N,et al.The association of DNA repair gene polymorphisms with the development and progression of renal cell carcinoma[J].Ann Oncol,2007,18(11):1817-1827.
[29] LIU Q J,SHEN H L,LIN J,et al.Synergistic roles of p53 and HIF1alpha in human renal cell carcinoma-cell apoptosis responding to the inhibition of mTOR and MDM2 signaling pathways[J].Drug Des Devel Ther,2016,10(1):745-755.
[30] WANG Z,PENG S,JIANG N,et al.Prognostic and clinicopathological value of p53 expression in renal cell carcinoma:a meta-analysis[J].Oncotarget,2017,8(60):102361-102370.