Mutation Status and Prognostic Value of KRAS and BRAF in Southeast Iranian Colorectal Cancer Patients: First Report from Southeast of Iran

J Gastrointest Cancer. 2021 Jun;52(2):557-568. doi: 10.1007/s12029-020-00426-8.

Abstract

Main purpose: This study aimed to determine any association of KRAS and BRAF mutations in colorectal cancer with clinicopathological features and overall survival (OS) of Southeast Iranian colorectal cancer (CRC) patients.

Methods: Overall, KRAS and BRAF status were assessed in 100 Iranian CRC subjects. A hundred consecutive stages I-IV CRC patients, who underwent surgical tumor resection from February 2012 to August 2015, were prospectively attained from three centers and were enrolled in the research. Direct sequencing and real-time PCR methods were used to the detection of KRAS and BRAF mutations, respectively. Logistic regression models were used to detect associations of KRAS and BRAF mutations with clinical/clinicopathological features. Kaplan-Meier model was used to estimate overall survival.

Results: In total, KRAS and BRAF mutations were detected in 29 (29%) and 7 (7%) of 100 CRC patients, respectively. BRAF mutations that all comprised V600E and KRAS mutations were found in codon 12, 13, and 61 (72.4%, 20.7 and 6.9%), respectively. In a multivariate analysis, older age (≥ 60) was significantly associated with higher KRAS mutations rate and high BRAF mutation rate was significantly associated with older age (≥ 60) and poorly differentiated tumors. KRAS and BRAF mutant vs. wild type of KRAS and BRAF, 5-year OS was 62.1% vs. 71.8% (p value > 0.05) and 57.1% vs. 67.7% (p value > 0.05), respectively.

Conclusion: Mutations were found in both KRAS and BRAF genes in Iranian colorectal cancers patients and were associated with clinical/clinicopathologic features. Our data emphasizes the importance of these molecular features in Iranian CRC patients.

Keywords: BRAF; Clinicopathological features; Colorectal cancer; KRAS; Overall survival; Southeast Iranian.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Cell Differentiation / genetics
  • Colon / pathology
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality*
  • Colorectal Neoplasms / pathology
  • DNA Mutational Analysis
  • Female
  • Humans
  • Iran / epidemiology
  • Kaplan-Meier Estimate
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Mutation
  • Prognosis
  • Prospective Studies
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Rectum / pathology
  • Risk Assessment / methods
  • Risk Factors
  • Young Adult

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)