Previous studies have suggested that cancer stem cells serve crucial functions in tumorigenesis, metastasis and therapy failure. Stem cell signaling transduction pathways are frequently dysregulated in cancer and associated with tumorigenesis, metastasis and the cell cycle, which are necessary for cancer proliferation. However, cancer stem cell-associated gene signatures have not been established for predicting patient outcomes in colorectal cancer. Using a gene-mining approach, the present study performed mRNA expression profiling in large colorectal cancer cohorts from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database, including a TCGA colorectal cancer cohort (n=383) and three independent validation series GSE39582 (n=582), GSE17536 (n=177) and GSE17537 (n=55). The present study identified that an eight-gene signature in cancer stem cell signaling was associated with the overall survival and disease/recurrence-free survival of patients with colorectal. On the basis of this signature, patients in the TCGA training sets were divided into high-risk and low-risk subgroups with a significantly different overall survival rate (hazard ratio, 2.38; P=0.0005). The prognostic value of this signature was confirmed using three independent GEO colorectal cancer sets. Identifying this prognostic stem cell signaling signature may provide an efficient classification tool for clinical prognosis evaluation, and facilitate cancer stem cell-targeted therapy.
Keywords: cancer stem cell; colorectal cancer; gene signature; prognosis.