KRAS/NRAS Mutations Associated with Distant Metastasis and BRAF/PIK3CA Mutations Associated with Poor Tumor Differentiation in Colorectal Cancer
- PMID: 37720173
- PMCID: PMC10503567
- DOI: 10.2147/IJGM.S428580
KRAS/NRAS Mutations Associated with Distant Metastasis and BRAF/PIK3CA Mutations Associated with Poor Tumor Differentiation in Colorectal Cancer
Abstract
Background: The occurrence, progression, and prognosis of colorectal cancer (CRC) are regulated by EGFR-mediated signaling pathways. However, the relationship between the core genes (KRAS/NRAS/BRAF/PIK3CA) status in the signaling pathways and clinicopathological characteristics of CRC patients in Hakka population remains controversial.
Methods: Patients were genotyped for KRAS (codons 12, 13, 61, 117, and 146), NRAS (codons 12, 61, 117, and 146), BRAF (codons 600), and PIK3CA (codons 542, 545 and 1047) mutations. Clinical records were collected, and clinicopathological characteristic associations were analyzed together with mutations of studied genes.
Results: Four hundred and eight patients (256 men and 152 women) were included in the analysis. At least one mutation in the four genes was detected in 216 (52.9%) patients, while none was detected in 192 (47.1%) patients. KRAS, NRAS, BRAF, and PIK3CA mutation status were detected in 190 (46.6%), 11 (2.7%), 10 (2.5%), 34 (8.3%) samples, respectively. KRAS exon 2 had the highest proportion (62.5%). Age, tumor site, tumor size, lymphovascular invasion, and perineural invasion were not associated with gene mutations. KRAS mutations (adjusted OR 1.675, 95% CI 1.017-2.760, P=0.043) and NRAS mutations (adjusted OR 5.183, 95% CI 1.239-21.687, P=0.024) appeared more frequently in patients with distant metastasis. BRAF mutations (adjusted OR 7.224, 95% CI 1.356-38.488, P=0.021) and PIK3CA mutations (adjusted OR 3.811, 95% CI 1.268-11.455, P=0.017) associated with poorly differentiated tumor.
Conclusion: KRAS/NRAS mutations are associated with distant metastasis and BRAF/PIK3CA mutations are associated with poor tumor differentiation in CRC. And the results provided a better understanding between clinicopathological characteristics and gene mutations in CRC patients.
Keywords: BRAF; KRAS; NRAS; PIK3CA; clinicopathological feature; colorectal cancer.
© 2023 Zeng et al.
Conflict of interest statement
The authors declare that they have no competing interests in this work.
Similar articles
-
Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer.Biomed Rep. 2023 Oct 31;19(6):104. doi: 10.3892/br.2023.1686. eCollection 2023 Dec. Biomed Rep. 2023. PMID: 38025833 Free PMC article.
-
Effectors of epidermal growth factor receptor pathway: the genetic profiling ofKRAS, BRAF, PIK3CA, NRAS mutations in colorectal cancer characteristics and personalized medicine.PLoS One. 2013 Dec 10;8(12):e81628. doi: 10.1371/journal.pone.0081628. eCollection 2013. PLoS One. 2013. PMID: 24339949 Free PMC article.
-
Relationship between mismatch repair protein, RAS, BRAF, PIK3CA gene expression and clinicopathological characteristics in elderly colorectal cancer patients.World J Clin Cases. 2021 Apr 16;9(11):2458-2468. doi: 10.12998/wjcc.v9.i11.2458. World J Clin Cases. 2021. PMID: 33889611 Free PMC article.
-
Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?Genet Med. 2013 Jul;15(7):517-27. doi: 10.1038/gim.2012.184. Epub 2013 Feb 21. Genet Med. 2013. PMID: 23429431
-
PIK3CA mutation and clinicopathological features of colorectal cancer: a systematic review and Meta-Analysis.Acta Oncol. 2020 Jan;59(1):66-74. doi: 10.1080/0284186X.2019.1664764. Epub 2019 Sep 23. Acta Oncol. 2020. PMID: 31545109
Cited by
-
The role of PIK3CA gene mutations in colorectal cancer and the selection of treatment strategies.Front Pharmacol. 2024 Oct 30;15:1494802. doi: 10.3389/fphar.2024.1494802. eCollection 2024. Front Pharmacol. 2024. PMID: 39555098 Free PMC article. Review.
-
Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer.Biomed Rep. 2023 Oct 31;19(6):104. doi: 10.3892/br.2023.1686. eCollection 2023 Dec. Biomed Rep. 2023. PMID: 38025833 Free PMC article.
-
TIM-3/Galectin-9 Immune Axis in Colorectal Cancer in Relation to KRAS, NRAS, BRAF, PIK3CA, AKT1 Mutations, MSI Status, and the Cytokine Milieu.Int J Mol Sci. 2025 Jul 14;26(14):6735. doi: 10.3390/ijms26146735. Int J Mol Sci. 2025. PMID: 40724985 Free PMC article.
-
Genomic Variants and Worldwide Epidemiology of Breast Cancer: A Genome-Wide Association Studies Correlation Analysis.Genes (Basel). 2024 Jan 23;15(2):145. doi: 10.3390/genes15020145. Genes (Basel). 2024. PMID: 38397135 Free PMC article.
-
Associations of SEMA7A, SEMA4D, ADAMTS10, and ADAM8 with KRAS, NRAS, BRAF, PIK3CA, and AKT Gene Mutations, Microsatellite Instability Status, and Cytokine Expression in Colorectal Cancer Tissue.Curr Issues Mol Biol. 2024 Sep 15;46(9):10218-10248. doi: 10.3390/cimb46090609. Curr Issues Mol Biol. 2024. PMID: 39329961 Free PMC article.
References
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous