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

J Clin Lab Anal. 2021 Mar;35(3):e23679. doi: 10.1002/jcla.23679. Epub 2020 Dec 9.

Abstract

Background: Despite 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.

Methods: B-Raf protein expression was identified by immunohistochemistry, while gene expression studies were quantified by real-time qPCR in 53 paired archived CRC specimens.

Results: The 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.

Keywords: BRAF; IHC; colorectal cancer; gene expression; miR-17; prognosis; qPCR.

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Pilot Projects
  • Prognosis
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Retrospective Studies
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MAS1 protein, human
  • MIRN17 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Mas
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf