Association of KRAS, NRAS, BRAF and PIK3CA gene mutations with clinicopathological features, prognosis and ring finger protein 215 expression in patients with colorectal cancer

Jing-Bo Wu; Xiao-Jing Li; Hui Liu; Yong-Juan Liu; Xiu-Ping Liu

doi:10.3892/br.2023.1686

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.

Authors

Jing-Bo Wu¹, Xiao-Jing Li¹, Hui Liu¹, Yong-Juan Liu¹, Xiu-Ping Liu²

Affiliations

¹ Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, P.R. China.
² Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, P.R. China.

Abstract

The relationships of KRAS, NRAS, BRAF and PIK3CA gene mutations with the clinicopathological features and prognosis of colorectal cancer (CRC) in patient are lacking. Furthermore, the role of ring finger protein 215 (RNF215) in CRC patients with KRAS, NRAS, BRAF and PIK3CA mutations remains unclear. In the present study, 182 surgical resection specimens from patients with primary CRC for retrospective analysis, were collected. KRAS/NRAS/BRAF/PIK3CA gene mutations were confirmed by an amplification-refractory mutation system. Immunohistochemistry (IHC) was conducted to confirm KRAS, NRAS, BRAF and PIK3CA protein expression. RNF215 expression in patients with CRC was evaluated using TIMER 2.0 database and IHC. The individual mutation rates of KRAS, NRAS, BRAF and PIK3CA were 40.7% (74/182), 4.4% (8/182), 4.4% (8/182) and 3.3% (6/182), respectively. The KRAS exon 2 mutation rate was the highest (61.5%, 64/104), and these mutations mainly occurred at codons 12 and 13. KRAS/NRAS/BRAF/PIK3CA wild-type CRC patients had significantly longer overall survival and disease-free survival than mutated KRAS/NRAS/BRAF/PIK3CA CRC patients (P<0.05). Overall, 45.4% (5/11) of patients with PIK3CA mutations had concomitant KRAS mutations. The KRAS/NRAS/BRAF/PIK3CA gene mutation rate in patients with lymph node metastasis (76.1%, 35/46) was significantly higher than that in patients without lymph node metastasis (50.8%, 69/136) (P=0.0027). There were no significant differences in IHC expression between patients with and without KRAS, NRAS, BRAF and PIK3CA mutations (P>0.05). The TIMER 2.0 analysis showed that RNF215 expression was significantly higher in the mutated BRAF group than in the wild-type BRAF group in CRC (P<0.05). In conclusion, KRAS is the most commonly mutated gene, and KRAS mutations may be a poor prognostic factor for patients with CRC. KRAS wild-type patient resistance may be related to PIK3CA gene mutations, although this needs further verification in larger cohorts. BRAF mutations may be associated with RNF215 expression in patients with CRC.

Keywords: BRAF; KRAS; NRAS proto-oncogene; PIK3CA; colorectal cancer; prognosis; ring finger protein 215.

Grants and funding

Funding: The present study was supported by the High-level Professional Physician Training Program of Minhang, Shanghai (grand no. 2020MZYS10) and the Natural Science Research Project of the Science and Technology Commission in Minhang, Shanghai (grand no. 2022MHZ043).