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miR-15a-5p, A Novel Prognostic Biomarker, Predicting Recurrent Colorectal Adenocarcinoma
Christos K Kontos1, Panagiotis Tsiakanikas1, Margaritis Avgeris1
1Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Panepistimiopolis, 15701, Athens, Greece.
Introduction:
Colorectal cancer is one of the most common gastrointestinal diseases and the second leading cause of cancer-associated deaths among adults. miR-15a-5p is a post-transcriptional regulator of the proto-oncogene MYB, a transcription factor essential for prolonged cancer cell proliferation and survival. In the current study, we assessed the potential diagnostic and prognostic utility of miR-15a-5p expression in colorectal adenocarcinoma.
Methods:
To accomplish this goal, total RNA was extracted from 182 colorectal adenocarcinoma specimens and 86 non-cancerous colorectal mucosae. After polyadenylation by poly(A) polymerase and subsequent reverse transcription with an oligo-dT adapter primer, miR-15a-5p expression was analyzed using an in-house developed reverse transcription quantitative real-time PCR method, based on SYBR Green chemistry. SNORD43 (RNU43) was used as an internal control gene.
Results:
miR-15a-5p was significantly upregulated in colorectal tumors compared to non-cancerous colorectal mucosae, while ROC analysis suggested its potential use for diagnostic purposes. Moreover, miR-15a-5p overexpression predicts poor disease-free survival (DFS) and overall survival (OS). Multivariate Cox regression analysis confirmed that miR-15a-5p overexpression is a significant unfavorable prognosticator of DFS in colorectal adenocarcinoma, independent of other established prognostic factors plus treatment of patients. Importantly, miR-15a-5p overexpression retains its unfavorable prognostic value in patients with T3 colorectal adenocarcinoma and in those without distant metastasis (M0). More importantly, the cumulative DFS probability of patients with early stage disease was significantly lower for those with colorectal adenocarcinoma overexpressing miR-15a-5p.
Discussion:
In conclusion, elevated expression of the cancer-associated miR-15a-5p predicts poor DFS and OS of colorectal adenocarcinoma patients. The prognostic value of miR-15a-5p expression regarding DFS is independent of clinicopathological factors currently used for colorectal adenocarcinoma prognosis.