Cell cycle related genes up-regulated in human colorectal development predict the overall survival of late-stage colorectal cancer patients

Abstract

A tumor can be perceived as a special “organ” that undergoes aberrant and poorly regulated organogenesis. Embryonic development and carcinogenesis share striking similarities in their cellular behavior and underlying molecular mechanisms. This intimate association makes embryonic development a viable reference model for studying cancer thereby circumventing the potentially misleading complexity of tumor heterogeneity. Therefore, on the basis of global expression profile, the genes simultaneously activated (up-regulated in terms of expression profile) or suppressed (down-regulated) in both the embryonic development and cancer stage, probably contain profound information on the molecular mechanism of cancer. In this study, the Affymetrix expression profile of 1593 colorectal cancer samples was downloaded from Gene Expression Omnibus. The 1396 differentially expressed probes were robustly obtained using 660 colorectal normal and cancer samples, the expression pattern of which was analyzed using our human colorectal developmental data. All of these 1396 probes were classified into 27 distinct patterns based on their expression patterns during the developmental process. By means of gene set enrichment analysis, we collected 393 V probes simultaneously up-regulated in both development and carcinogenesis and 207 A probes down-regulated in both. Functional enrichment analysis indicated that the V probes were significantly related to cell cycle regulation. Notably, 28 cell-cycle related probes within the V probe group were found to be significantly associated with an overall survival of Stage III/IV patients (GSE17536 cross validation, n = 96, p = 5.70 × 10⁻³; GSE29621, n = 36, p = 1.70 × 10⁻³; GSE39084, n = 38, p = 0.05; GSE39582, n = 264, p = 0.047; GSE17537, n = 36, p = 5.90 × 10⁻³).