Identification of a sixteen-microRNA signature as prognostic biomarker for stage II and III colon cancer
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Havjin Jacob1, Luka Stanisavljevic2, Kristian Eeg Storli3, Kjersti E. Hestetun1, Olav Dahl1,2 and Mette P. Myklebust2
1Department of Clinical Science, Faculty of Medicine, University of Bergen, Bergen, Norway
2Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway
3Department of Surgery, Haraldsplass Deaconess Hospital, Bergen, Norway
Havjin Jacob, email: [email protected]
Keywords: miRNA, signature, colon cancer, recurrence, RT-qPCR
Received: June 29, 2017 Accepted: August 25, 2017 Published: September 23, 2017
Despite advances in colon cancer research and novel therapies, high risk of recurrence remains a major challenge. This study reports miRNA expression profiling as a biomarker for the prognosis of TNM stage II and III colon cancer.
Fresh frozen biopsies from the study cohort (N=111) were analyzed for miRNA by RT-qPCR and LASSO regression analysis was used to build a classifier of miRNAs. The prognostic accuracy was tested and the classifier was validated in an independent colon cohort (TCGA-COAD, N=209).
The LASSO regression analysis identified a 16-miRNA signature including miR-143-5p, miR-27a-3p, miR-31-5p, miR-181a-5p, miR-30b-5p, miR-30d-5p, miR-146a-5p, miR-23a-3p, miR-150-5p, miR-210-3p, miR-25-3p, miR-196a-5p, miR-148a-3p, miR-222-3p, miR-30c-5p and miR-223-3p. A low 16-miRNA signature was associated with better 5-year disease-free survival (DFS) in the study cohort than a high signature (93 % versus 58 %; p< 0.001). The signature was an independent prognostic factor for better 5-year DFS in multivariate analyses (HR 21.4; 95% CI: 4.21-108.7; p< 0.001). The results in the validation cohort were consistent with the study cohort in univariate (77 % versus 65 %; p= 0.045) and multivariate analyses (HR 2.0; 95% CI: 1.04-3.89; p=0.039).
We identified a 16-miRNA signature as a reliable prognostic biomarker for classification of colon cancer stage II and III patients into groups with low and high risk for recurrence.
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