Prognostic value of BRAF/MIR-17 signature and B-Raf protein expression in patients with colorectal cancer: A pilot study.

Abstract

BackgroundDespite the recent improvement in colorectal cancer (CRC) treatment, it still has a poor prognosis with a low survival rate. Genetic and epigenetic mechanisms have proved to play a substantial role in CRC tumorigenesis and progression. According to Gene Ontology and TargetScan analyses, the B‐Raf proto‐oncogene (BRAF) gene is one of the microRNA‐17 (miR‐17) targets. We aimed to explore the prognostic value of B‐Raf protein and BRAF/microRNA‐17 (MIR‐17) gene expression signature in CRC archived samples.MethodsB‐Raf protein expression was identified by immunohistochemistry, while gene expression studies were quantified by real‐time qPCR in 53 paired archived CRC specimens.ResultsThe BRAF showed higher expressions in CRC specimens relative to non‐cancer tissues (p = 0.006). MIR17 expression was inversely and significantly correlated with both B‐Raf protein (r = −0.79, p < 0.001) and gene expression (r = −0.35, p = 0.010) and showed a significant direct correlation with a high rate of relapse (p = 0.020). BRAF/miR‐17 expression in CRC was associated inversely with tumor size, high grade of colonic carcinoma, lymph node metastasis, and carcinoma subtype. Spearman correlation and Kaplan‐Meier survival curve analyses revealed that disease‐free survival and overall survival were inversely and significantly correlated with positive B‐Raf protein expression (r = −0.31 and −0.35, p = 0.023 and 0.011, respectively) and directly correlated with log BRAF/MIR17 ratio (r = 0.50 and 0.41, p < 0.001 and = 0.003, respectively). Cox hazard regression analysis revealed the BRAF/MIR17 ratio could predict both types of patients' survival, among other variables.Conclusion BRAF/MIR17 ratio could have prognostic utility in patients with CRC. Further larger‐scale studies are warranted to confirm this utility.