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

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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.

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Acknowledgments

The authors thank Mohammad Ali Mohammadi (Ph.D. candidate in Biomedicine, Kerman University of Medical Sciences, Iran) for molecular testing guidance.

Funding

This study was supported by the research fund of Kerman University of Medical Sciences (project No. 97000217).

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A.Y conceived and designed the study. A. Y, A.S, Z.M.K and N.K.K performed the experiments and data analysis. A.Y and A.A interpreted the data and drafted the manuscript. M.S.F and Z.M.K helped with sample preparation, patient’s data collection and interpretation. A.Y and M.R.Z helped with statistical analysis. S.D. supervised the findings of this work, reviewed and revised the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Shahriar Dabiri.

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The Ethical Committee of the Kerman University of Medical Sciences approved this research (Approval No. IR.KMU.REC.1397.209).

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Yari, A., Samoudi, A., Afzali, A. et al. Mutation Status and Prognostic Value of KRAS and BRAF in Southeast Iranian Colorectal Cancer Patients: First Report from Southeast of Iran. J Gastrointest Canc 52, 557–568 (2021). https://doi.org/10.1007/s12029-020-00426-8

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