Analysis of KRAS, NRAS, and BRAF Mutations, Microsatellite Instability, and Relevant Prognosis Effects in Patients With Early Colorectal Cancer: A Cohort Study in East Asia

Abstract

BackgroundEarly colorectal cancer (ECRC) refers to any size of colorectal cancer (CRC) whose depth of invasion is limited to the mucosa and submucosa. About 10% of patients with ECRC die from cancer after surgery. KRAS, NRAS, and BRAF mutations and microsatellite instability (MSI) are considered diagnostic and prognostic markers in CRC. However, their characteristics in ECRC and whether postoperative chemotherapy based on them will benefit ECRC patients or not remain unknown.Patients and MethodsPatients with ECRC and 298 patients with advanced colorectal cancer (ACRC) were collected in our hospital from January 2013 to December 2015. The Amplification Refractory Mutation System (ARMS)-PCR was used to perform the KRAS, NRAS, and BRAF mutant tests.ResultsIn ECRC patients, 43 cases of KRAS mutation were found, accounting for 69.35%. Interestingly, among KRAS mutations, there were 10 KRAS multi-site mutation patients (16.13% in 62 ECRC patients). Moreover, the NRAS mutation rate was 3.23% but no BRAF mutation was found and only 1 case of MSI-High was detected. KRAS mutation was only related to the depth of tumor invasion whereas KRAS multi-site mutations were related to mucus components and tumor size. As far as NRAS is concerned, mutations were associated with elevated CEA, mucus components, and the depth of tumor invasion. Notably, compared with 2.35% KRAS multi-site mutation in ACRC, the rate of KRAS multi-site mutation in ECRC was much higher. Furthermore, Cox regression analysis revealed that KRAS mutation could be an independent prognostic factor of ECRC in patients who have undergone endoscopic resection or surgery.ConclusionPatients with ECRC might benefit from KRAS mutation testing but not from postoperative chemotherapy.

High Probability of Lynch Syndrome among colorectal cancer patients in Indonesia is associated with higher occurrence of KRAS and PIK3CA mutations

“…Distinct mutations located in codons 13, 14, 34, 58, 59, and 146 were found as opposed to more commonly reported mutations in codons 12, 13, 61, 146 [42][43][44]. A recent study in China has also reported that KRAS mutation was found in 69.4% of the early lesions [45,46]. Furthermore, in this study, we found that the KRAS mutation was enriched in MSI compared to MSS cases (76.19% and 58.91%, respectively).…”

“…Distinct mutations located in codons 13, 14, 34, 58, 59, and 146 were found as opposed to more commonly reported mutations in codons 12, 13, 61, 146 [42–44]. A recent study in China has also reported that KRAS mutation was found in 69.4% of the early lesions [45, 46].…”

Differential Perspectives by Specialty on Oligometastatic Colorectal Cancer: A Korean Oligometastasis Working Group’s Comparative Survey Study

“…KRAS mutations are detected in 40%–50% of the colorectal cancer patients and known as poor prognostic indicators [ 20 , 21 ]. BRAF mutations account for approximately 4%–10% of the colorectal cancer patients and are also associated with poor prognosis [ 22 ]. Another widely reported biomarker for colorectal cancer is MSI or TP53 [ 23 ].…”

The role of heavy metals in the development of colorectal cancer

“…Studies have shown that CRC patients with MSI have a better prognosis compared to MSS [ 31 , 53 ]. BRAF is a downstream gene of RAS in the RAS-RAF-MAPK signaling pathway, BRAF V600E mutation leads to uncontrolled cell proliferation, migration, escape from apoptosis and angiogenesis [ 54 , 55 ]. Research showed that BRAF is associated with poor prognosis in CRC patients, especially in BRAF V600E MSS patients [ 56 – 58 ].…”