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Prognostic Value of BRAF and KRAS Mutation in Relation to Colorectal Cancer Survival in Iranian Patients: Correlated to Microsatellite Instability

  • Ehsan Nazemalhosseini-Mojarad
  • Roya Kishani Farahani
  • Maryam Mehrizi
  • Kaveh Baghaei
  • Mohammad Yaghoob Taleghani
  • Mina Golmohammadi
  • Noshad Peyravian
  • Sara AshtariEmail author
  • Mohmad Amin Pourhoseingholi
  • Hamid Asadzadeh Aghdaei
  • Mohammad Reza Zali
Original Research
  • 20 Downloads

Abstract

Purpose

To evaluate the prognostic role of BRAF and KRAS mutations after adjustment for microsatellite instability (MSI) in Iranian colorectal cancer (CRC) patients.

Methods

BRAF and KRAS mutations and MSI status were assessed in 258 Iranian subjects with CRC. Two hundred fifty-eight consecutive stages I-IV CRC patients, who underwent surgical resection of adenocarcinoma from 2012 to 2016, were enrolled in the research. Pyrosequencing and Cast-PCR methods were used to the detection of KRAS and BRAF mutations. Kaplan-Meier and Cox regression were employed to estimate hazard ratios (HR) for the association between BRAF and KRAS mutation and overall survival (OS).

Results

KRAS and BRAF mutations were detected in 36 (14%) and 15 (5.8%) cases of 258 patients with CRC, respectively. BRAF mutations that all comprised V600E and KRAS mutations was found in codon 12 and 13 (80.6% and 19.4%), respectively. KRAS mutations were detected in 19 (15.4%) patients of 123 microsatellite stable (MSS) CRC and it is significantly associated with tumor location and metastasis. BRAF and KRAS mutant vs. wild type of BRAF and KRAS, 5-year OS was 73.3% vs. 82.3% and 83.3% vs. 81.5% (long-rank P > 0.05), respectively. KRAS mutant vs. KRAS-wild-type tumors in MSS/MSI-L status CRC patients, 5-year OS was 78.9% vs. 90.4% (long-rank p = 0.046).

Conclusion

The present study revealed that BRAF and KRAS mutations were not related to the worse overall survival, while KRAS mutation can be a prognostic factor for overall survival in sporadic microsatellite-stable (MSS) status in Iranian CRC patients.

Keywords

KRAS BRAF Survival Colorectal cancer Prognostic value Iran 

Notes

Acknowledgments

This study was performed in Shahid Beheshti University of Medical Sciences and supported by grant number 8910.

Funding

This project was completely supported and funded by Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences and Medical Ethical committee of RCGLD with the Ethic NO: IR.SBMU.RIGLD. REG.1391.681.

Compliance with Ethical Standards

The Ethical Committee of the Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, approved this research (IR.SBMU.RIGLD.REC.1396.681).

Conflict of Interest

The authors declare that they have no conflict of interest.

Disclosure Statement

The authors have nothing to disclose.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Ehsan Nazemalhosseini-Mojarad
    • 1
  • Roya Kishani Farahani
    • 1
  • Maryam Mehrizi
    • 1
  • Kaveh Baghaei
    • 2
  • Mohammad Yaghoob Taleghani
    • 1
  • Mina Golmohammadi
    • 1
  • Noshad Peyravian
    • 1
  • Sara Ashtari
    • 2
    Email author
  • Mohmad Amin Pourhoseingholi
    • 2
  • Hamid Asadzadeh Aghdaei
    • 2
  • Mohammad Reza Zali
    • 2
  1. 1.Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver DiseasesShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Taleghani HospitalShahid Beheshti University of Medical SciencesTehranIran

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