A 65-gene signature for prognostic prediction in colon adenocarcinoma

作者：Jiang, Hui; Du, Jun; Gu, Jiming; Jin, Liugen; Pu, Yong; Fei, Bojian^*

来源：International Journal of Molecular Medicine, 2018, 41(4): 2021-2027.

DOI：10.3892/ijmm.2018.3401

• colon adenocarcinoma
• gene signature
• co-expression network
• differentially expressed genes
• prognostic prediction system

The aim of the present study was to examine the molecular factors associated with the prognosis of colon cancer. Gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus databases to screen differentially expressed genes (DEGs) between colon cancer samples and normal samples. Survival-related genes were selected from the DEGs using the Cox regression method. A co-expression network of survival-related genes was then constructed, and functional clusters were extracted from this network. The significantly enriched functions and pathways of the genes in the network were identified. Using Bayesian discriminant analysis, a prognostic prediction system was established to distinguish the positive from negative prognostic samples. The discrimination efficacy of the system was validated in the GSE17538 dataset using Kaplan-Meier survival analysis. A total of 636 and 1,892 DEGs between the colon cancer samples and normal samples were screened from the TCGA and GSE44861 dataset, respectively. There were 155 survival-related genes selected. The co-expression network of survival-related genes included 138 genes, 534 lines (connections) and five functional clusters, including the signaling pathway, cellular response to cAMP, and immune system process functional clusters. The molecular function, cellular components and biological processes were the significantly enriched functions. The peroxisome proliferator-activated receptor signaling pathway, Wnt signaling pathway, B cell receptor signaling pathway, and cytokine-cytokine receptor interactions were the significant pathways. A prognostic prediction system based on a 65-gene signature was established using this co-expression network. Its discriminatory effect was validated in the TCGA dataset (P=3.56e-12) and the GSE17538 dataset (P=1.67e-6). The 65-gene signature included kallikrein-related peptidase 6 (KLK6), collagen type XI 1 (COL11A1), cartilage oligomeric matrix protein, wingless-type MMTV integration site family member 2 (WNT2) and keratin 6B. In conclusion, a 65-gene signature was screened in the present study, which showed a prognostic prediction effect in colon adenocarcinoma. KLK6, COL11A1, and WNT2 may be suitable prognostic predictors for colon adenocarcinoma.

• 出版日期2018-4
• 单位江南大学