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基于生物信息学分析的结直肠腺癌预后生物标志物及药物靶点鉴定

Identification of Prognostic Biomarkers and Drugs Targeting Them in Colon Adenocarcinoma: A Bioinformatic Analysis.

机构信息

1 Fudan University Shanghai Cancer Center, Shanghai, China.

2 Shanghai Medical College, Fudan University, Shanghai, China.

出版信息

Integr Cancer Ther. 2019 Jan-Dec;18:1534735419864434. doi: 10.1177/1534735419864434.

Abstract

To identify prognostic biomarkers and drugs that target them in colon adenocarcinoma (COAD) based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases. The TCGA dataset was used to identify the top 50 upregulated differentially expressed genes (DEGs), and Gene Expression Omnibus profiles were used for validation. Survival analyses were conducted with the TCGA dataset using the RTCGAToolbox package in the R software environment. Drugs targeting the candidate prognostic biomarkers were searched in the DrugBank and herbal databases. Among the top 50 upregulated DEGs in patients with COAD in the TCGA dataset, the Wnt signaling pathway and cytokine-cytokine receptor interactions and pathways in cancer Kyoto Encyclopedia of Genes and Genomes pathway analysis were enriched in DEGs. Tissue development and regulation of cell proliferation were the main Gene Ontology biological processes associated with upregulated DEGs. MYC and KLK6 were overexpressed in tumors validated in the TCGA, GSE41328, and GSE113513 databases (all < .001) and were significantly associated with overall survival in patients with COAD ( = .021 and = .047). Nadroparin and benzamidine were identified as inhibitors of MYC and KLK6 in DrugBank, and 8 herbs targeting MYC, including (), (), (), (), (), (), (), and (), were identified. MYC and KLK6 may serve as candidate prognostic predictors and therapeutic targets in patients with COAD.

摘要

基于癌症基因组图谱(TCGA)和基因表达综合数据库,鉴定结直肠腺癌(COAD)的预后生物标志物及靶向它们的药物。使用 TCGA 数据集鉴定前 50 个上调的差异表达基因(DEGs),并使用基因表达综合数据库进行验证。使用 TCGA 数据集的 RTCGAToolbox 软件包在 R 软件环境中进行生存分析。在 DrugBank 和草药数据库中搜索针对候选预后生物标志物的药物。在 TCGA 数据集的 COAD 患者中,前 50 个上调的 DEG 中,Wnt 信号通路和细胞因子-细胞因子受体相互作用及癌症京都基因与基因组百科全书通路分析中的途径在 DEG 中富集。组织发育和细胞增殖的调节是与上调的 DEG 相关的主要基因本体生物学过程。在 TCGA、GSE41328 和 GSE113513 数据库中验证,MYC 和 KLK6 在肿瘤中过度表达(均<0.001),并与 COAD 患者的总生存期显著相关(=0.021 和=0.047)。在 DrugBank 中,纳曲肝素和苯甲脒被鉴定为 MYC 和 KLK6 的抑制剂,针对 MYC 的 8 种草药,包括()、()、()、()、()、()、()和(),被鉴定出来。MYC 和 KLK6 可能成为 COAD 患者的候选预后预测因子和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3271/6681251/ff13f8b491f0/10.1177_1534735419864434-fig1.jpg

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