KRAS/NRAS Mutations Associated with Distant Metastasis and BRAF/PIK3CA Mutations Associated with Poor Tumor Differentiation in Colorectal Cancer

Juanzi Zeng,1,2 Wenwei Fan,3 Jiaquan Li,1,2 Guowu Wu,1,2 Heming Wu2 1Department of Medical Oncology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gastroenterology, Dongguan Eighth People’s Hospital, Dongguan, People’s Republic of ChinaCorrespondence: Heming Wu, Center for Precision Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email wuheming1986@126.comBackground: 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: colorectal cancer, KRAS, NRAS, BRAF, PIK3CA, clinicopathological feature