Hypoxia has been particularly associated with poor prognosis in
cancer patients. Recent studies have suggested that
hypoxia-related
miRNAs play a critical role in various
cancers, including
colorectal cancer (CRC). In the present study, we found 52 differentially expressed
miRNAs in HT-29 cells under hypoxic conditions versus normoxic conditions by analyzing the profiles of
miRNAs. Using Cox model, we developed a
hypoxia-related
miRNA signature consisting of four
miRNAs, which could successfully discriminate high-risk patients in the
Cancer Genome Atlas (TCGA) training cohort (n=381). The prognostic value of this signature was further confirmed in the TCGA testing cohort (n=190) and an independent validation cohort composed of
formalin-fixed
paraffin-embedded clinical CRC samples (n=220), respectively. Multivariable Cox regression and stratified survival analysis revealed this signature was an independent prognostic factor for CRC patients. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of this signature was significantly larger than that of any other clinical risk factors or single
miRNA alone. A nomogram was constructed for clinical use, which incorporated both the
miRNA signature and clinical risk factors and performed well in the calibration plots. Collectively, this novel
hypoxia-related
miRNA signature was an independent prognostic factor, and it possessed a stronger predictive power in identifying high-risk CRC patients than currently used clinicopathological features.