Identification of Prognostic Biomarkers and Drugs Targeting Them in Colon Adenocarcinoma: A Bioinformatic Analysis. (August 2019)

• Record Type: Journal Article
• Authors: Dong, Shu; Ding, Zhimin; Zhang, Hao; Chen, Qiwen
• Is Part Of: Integrative cancer therapies. Volume 18(2019)
• Publication Date: 2019-08
• Subjects: colon adenocarcinoma -- colorectal carcinoma -- MYC -- kallikrein-related peptidase -- KLK6; Cancer -- Alternative treatment -- Periodicals; 616.99406
• DOI: 10.1177/1534735419864434
• Languages: English
• ISSNs: 1534-7354

Abstract

Objective: 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.Methods: 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.Results: 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 P < .001) and were significantly associated with overall survival in patients with COAD ( P = .021 and P = .047). Nadroparin and benzamidine were identified as inhibitors of MYC and KLK6 in DrugBank, and 8 herbs targeting MYC, including Da Huang ( Radix Rhei Et Rhizome ), Hu Zhang ( Polygoni Cuspidati Rhizoma Et Radix ), Huang Lian ( Coptidis Rhizoma ), Ban Xia ( Arum Ternatum Thunb ), Tu Fu Ling ( Smilacis Glabrae Rhixoma ), Lei Gong Teng ( Tripterygii Radix ), Er Cha ( Catechu ), and Guang Zao ( Choerospondiatis Fructus ), were identified.Conclusion: MYC and KLK6 may serve as candidate prognostic predictors and therapeutic targets in patients with COAD.