MiR-31-5p-DMD axis as a novel biomarker for predicting the development and prognosis of sporadic early-onset colorectal cancer.

Abstract

The incidence of colorectal cancer (CRC) is increasing in young adults, but knowledge regarding the molecular features of sporadic early-onset colorectal cancer (SEOCRC) is limited. The objective of the present study was to investigate potential key tumorigenesis-associated genes and their regulatory microRNAs (miRNAs) in SEOCRC. Using miRNA and mRNA expression screening of SEOCRC and sporadic late-onset colorectal cancer (SLOCRC) by next generation sequencing (NGS) and bioinformatics, the SEOCRC-associated miRNAome and transcriptome were analyzed. In SEOCRC miRNA and mRNA expression profiles, the tumorigenesis-associated genes and their regulatory miRNAs were analyzed according to the miRTarBase database, and specific miRNA-mRNA pairs were selected as the candidate biomarkers in SEOCRC, which were further verified in another cohort of SEOCRC and SLOCRC patients' colon cancer and paracancerous tissues using reverse transcription-quantitative PCR and immunohistochemistry. Moreover, the clinical relevance of these paired signatures to clinicopathological features was determined in 80 patients with SEOCRC. The expression of dystrophin (DMD) was downregulated and that of miR-31-5p was upregulated in SEOCRC tissue compared with adjacent peritumoral tissue. While DMD and miR-31-5p were not differentially expressed in SLOCRC tissues compared with that in adjacent peritumoral tissues. The miR-31-5p-DMD axis was identified as the key regulatory axis specific to SEOCRC, and DMD expression was closely associated with TNM stage and lymph node metastasis. Importantly, Kaplan-Meier analysis revealed that patients with low DMD expression had significantly poorer overall survival, cancer specific survival and recurrence free survival compared with those with high expression of DMD. In conclusion, the miR-31-5p-DMD axis may serve as a novel biomarker in predicting the development of SEOCRC, and DMD can be used as a promising biomarker for the prognosis of SEOCRC.