Background: Colon cancer is one of the most common cancers with increasing incidence and high mortality worldwide. Prognosis and choice of treatment is largely based on the tumor stage at presentation. Thus, finding novel biomarkers for predicting survival is highly desirable. Lately, several studies have been looking at microRNAs (miRNAs) in several cancers, including colon cancer. MicroRNAs are conserved, non-coding RNA molecules that play an important role in the regulation of post-transcriptional gene expression.
Material and Methods: In the present study, we have profiled miRNA in one hundred and seventy two TNM stage I-IV colon cancer patients and 10 corresponding normal colon tissue samples. Total RNA was extracted from freshly frozen tissues, and the expression of miRNA profile were assessed using Pick and Mix focus panels from Exiqon containing 84 miRNAs that have been linked to cancer.
Results: The results were visualized in a heatmap (Qlucore omics Software) and more than 20 miRNAs were found to be differentially expressed in tumors compared to the normal colon. Further, twelve miRNAs were found to discriminate between relapse and no-relapse patients in TNM- stage II and III, and four of these miRNAs (miR-23a, miR-25, miR-30d and miR-31) were found to be statistically significant in binary logistic regression with relapse as outcome variable. In univariate analysis, low expression of the four-miRNA signature was associated with better 3-year disease-free survival (DFS), 88 % versus 63% in low versus high signature, respectively (P=0.001). Moreover, the signature was a predictor of poor relapse-free survival in multivariate analyses (P=0.001; HR 31; 95% CI: 3.8-248.9). Another regression analyses method (LASSO) identified a 16-miRNA signature, and the four miRNAs found earlier were among them. The 16-miRNA signature was associated with better survival (P<0.001).
Conclusion: The present study has identified a four-miRNA signature predicting relapse in colon cancer stage II and III patients.
Citation Format: Havjin Jacob, Luka Stanisavljevic, Kristian Eeg Storli, Olav Dahl, Mette Pernille Myklebust. Microrna signature as a potential biomarker for predicting survival in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 469. doi:10.1158/1538-7445.AM2017-469