Peer Review #2 of "Comprehensive analysis of metastasis-related genes reveals a gene signature predicting the survival of colon cancer patients (v0.2)"

Abstract

Objective The mechanism underlying colon cancer metastasis remain unclear. This study aimed to elucidate the genes alteration during the metastasis of colon cancer and identify genes that crucial to the metastasis and survival of colon cancer patients. Methods The dataset of primary and metastasis tissue of colon cancer, and dataset of high and low metastasis capability of colon cancer cells were selected as training cohort, and the overlapped differentially expressed genes (DEGs) were screened from the training cohort. The functional enrichment analysis for the overlapped DEGs was performed. The prognostic value of overlapped DEGs were analyzed in TCGA dataset, and a gene signature was developed using genes that related to the overall survival (OS). The prognostic value of the gene signature was further confirmed in a validation cohort. Results 184 overlapped DEGs were screened from the training cohort. Functional enrichment analysis revealed the significant gene functions and pathways of the overlapped DEGs. Four hub genes (OXCT1, ACTN4, IL-8, ITGA3) were identified using protein-protein network analysis. Six genes (ALDH2, NEDD9, FLNA, LBR, TWF1, SRSF1) were closely related to the OS of colon cancer patients. A gene signature was developed used these six genes based on their risk score, and the validation cohort indicated that the prognostic value of this gene signature was high in the prediction of colon cancer patients. Conclusions Our study demonstrates a gene profiles related to the metastasis of colon cancer, and identify a sixgene signature that acts as an independent biomarker on the prognosis of colon cancer.