基于癌症基因组图谱数据库的结直肠腺癌加权基因共表达网络的构建与分析
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摘要
目的利用癌症基因组图谱(TCGA)数据库结直肠腺癌组织样本表达谱数据,筛选差异表达的基因及微小RNA(miRNA),构建结直肠癌加权基因共表达网络,分析预后相关基因及miRNA。方法首先在TCGA数据库下载结直肠腺癌组织样本表达谱数据,应用生物信息学原理探索并分析差异表达基因及miRNA,构建加权基因共表达网络,筛选其枢纽基因及相关miRNA,进而发现预后相关枢纽基因及miRNA。结果共发现2个核心网络,结合2个核心网络的top10枢纽基因及相关miRNA,进一步确定了和预后相关的基因及miRNA,分别为CYP2E1和mir-885。结论构建结直肠癌加权基因共表达网络可为研究结直肠癌的潜在发病机制提供了参考,枢纽基因及相关miRNA有可能作为诊断的生物标志物和治疗靶点应用于临床。
Objective To screen differentially-expressed genes and miRNA,construct a co-expression network of weighted genes for colorectal cancer and finally to analyze prognosis-associated genes and miRNAs,by using the expression profile data of colorectal adenocarcinoma tissue samples from the Cancer Genome Atlas( TCGA) database. Methods Firstly,the expression profile data of colorectal adenocarcinoma tissue were downloaded from the TCGA database. The differentially-expressed genes and miRNAs were explored and analyzed using the principle of bioinformatics,and the weighted gene co-expression networks were constructed. The hub genes and related miRNAs were screened,and the prognostic related hub genes and miRNAs were found in the end. Results Revealed through study were a total of 2-core networks associated with the top10 hub genes and miRNAs of the two core networks,and the genes and miRNAs associated with the prognosis were further identified,which were CYP2E1 and mir-885,respectively. Conclusion The Construction of colorectal cancer weighted gene co-expression network could provide evidence for further study of potential pathogenesis of colorectal cancer. Hub genes and related miRNAs might be used as diagnostic biomarkers and therapeutic targets in clinical applications.
Objective To screen differentially-expressed genes and miRNA,construct a co-expression network of weighted genes for colorectal cancer and finally to analyze prognosis-associated genes and miRNAs,by using the expression profile data of colorectal adenocarcinoma tissue samples from the Cancer Genome Atlas( TCGA) database. Methods Firstly,the expression profile data of colorectal adenocarcinoma tissue were downloaded from the TCGA database. The differentially-expressed genes and miRNAs were explored and analyzed using the principle of bioinformatics,and the weighted gene co-expression networks were constructed. The hub genes and related miRNAs were screened,and the prognostic related hub genes and miRNAs were found in the end. Results Revealed through study were a total of 2-core networks associated with the top10 hub genes and miRNAs of the two core networks,and the genes and miRNAs associated with the prognosis were further identified,which were CYP2E1 and mir-885,respectively. Conclusion The Construction of colorectal cancer weighted gene co-expression network could provide evidence for further study of potential pathogenesis of colorectal cancer. Hub genes and related miRNAs might be used as diagnostic biomarkers and therapeutic targets in clinical applications.
引文
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[3]Huang Y,Zhou J,Luo S,et al.Identification of a fluorescent small-molecule enhancer for therapeutic autophagy in colorectal cancer by targeting mitochondrial protein translocase TIM44[J].Gut,2018,67(2):307-319.DOI:10.1136/gutjnl-2016-311909.
[4]Shen L,Qu X,Li H,et al.NDRG2 facilitates colorectal cancer differentiation through the regulation of Skp2-p21/p27 axis.[J].Oncogene,2018,37(13):1759-1774.DOI:10.1038/s41388-017-0118-7.
[5]Orang AV,Barzegari A.MicroRNAs in colorectal cancer:from diagnosis to targeted therapy.[J].Asian Pacific J Can Preven Apjcp,2014,15(17):6989-6999.DOI:10.7314/APJCP.2014.15.17.6989.
[6]Bi DP,Yin CH,Zhang XY,et al.MiR-183 functions as an oncogene by targeting ABCA1 in colon cancer[J].Oncol Rep,2016,35(5):2873-2879.DOI:10.3892/or.2016.4631.
[7]Network CGA.Comprehensive molecular characterization of human colon and rectal cancer.[J].Nature,2012,487(7407):330-337.DOI:10.1038/nature11252.
[8]Hu L,Chen HY,Cai J,et al.Serine threonine tyrosine kinase 1is a potential prognostic marker in colorectal cancer.[J].Bmc Cancer,2015,15(1):246.DOI:10.1186/s12885-015-1285-y.
[9]Hao M,Shu Z,Sun H,et al.GRIM-19 expression is a potent prognostic marker in colorectal cancer.[J].Human Pathol,2015,46(12):1815-1820.DOI:10.1016/j.humpath.2015.07.020.
[10]Sun H,Wang C,Miao H,et al.CYP24A1 is a potential biomarker for the progression and prognosis of human colorectal cancer[J].Human Pathol,2016,50:101-108.DOI:10.1016/j.humpath.2015.11.008.
[11]Peng H,Xie SK,Huang MJ,et al.Associations of CYP2E1rs2031920 and rs3813867 polymorphisms with colorectal cancer risk:a systemic review and meta-analysis.[J].Tumor Biol,2013,34(4):2389-2395.DOI:10.1007/s13277-013-0788-x.
[12]Xiao F,Qiu H,Cui H,et al.MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP/Smad/Id1 signaling[J].Oncogene,2015,34(15):1968-1978.DOI:10.1038/onc.2014.134.
[13]张竹红.miR-885-5p在肿瘤生长和转移中作用机制的研究[D].南开大学,2013.
[14]Afanasyeva EA,Mestdagh P,Kumps C,et al.MicroRNA miR-885-5p targets CDK2 and MCM5,activates p53 and inhibits proliferation and survival.[J].Cell Death Differ,2011,18(6):974-984.DOI:10.1038/cdd.2010.164.