Mutations in KRAS codon 12 predict poor survival in Chinese patients with metastatic colorectal cancer

Abstract

Abstract. KRAS mutations serve a function in tumorigenesis of colorectal cancer (CRC) and guide the use of targeted drugs. However, the prognostic value of KRAS mutations and their subtypes remain controversial. The present study aimed to investigate the correlations between KRAS mutations and clinicopathological characteristics, and their prognostic significance in Chinese patients with metastatic CRC (mCRC). A total of 135 patients with mCRC were analyzed for KRAS mutations. Mutations in codon 12 and 13 were identified in 45 (33.3%) patients. Only 3 patients harbored a mutation of V600E. Compared with male patients, KRAS codon 12 mutations were more common in female patients (P<0.05). KRAS codon 13 mutations tended to arise in right-sided compared with left-sided colon cancer (P<0.05). Survival analysis was performed in 101 patients receiving primary tumor resection. Compared with KRAS codon 12 wild-type, codon 12 mutations were markedly correlated with a poorer survival (log-rank P= 0.002). No prognostic significance was revealed in codon 13 mutations. In univariate analysis, mortality risk was significantly increased by subtypes of G12D and G12V [hazard ratio (HR) =2.313, 95% confidence interval (CI) =1. P=0.03; HR=2.621, P=0.04, respectively]. The results of the present study suggested that codon 12 mutations, in particular G12D and G12V, predicted a negative prognosis in Chinese patients with mCRC. These findings require further confirmation via prospective studies with larger samples.

Clinicopathological characteristics and mutational profile of KRAS and NRAS in Tunisian patients with sporadic colorectal cancer

“…In accordance with preceding reports, 90% of KRAS mutations found in our cohort are located in codons 12 and 13, where the majority occurred in codon 12 (85%) and (15%) 10 in codon 13 and most frequently observed types of mutations are G>A transitions and G>T transversions [14,16,31,[34][35][36].…”

“…Approximately 90% of KRAS mutations are located in codons 12 and 13 [11,14]. They are mostly single nucleotide point mutations, particularly G>A transitions and G>T transversions [15,16].…”

Survival Outcomes of Metastatic Colorectal Cancer Patients in Brunei Darussalam and the Impact of <em>KRAS</em> Mutations

“…There is a lack of data for the median survival periods of mutant KRAS mCRC patients with G12A, G12V and G12C mutations due to the small population. In codon 13, G13D is the most common KRAS mutation [15,50] and this was the second most common specific KRAS mutation after G12D in our study with a survival median period of 29 (95% CI:24.2-33.6) months (Table 4). Similar to most studies, we obtained that mutant KRAS mCRC patient mutation in codon 13 had a comparably better OS than those with mutation in codon 12 [14,50,52].…”

“…85% of KRAS mutation occurs in codons 12 and 13. Codons G12V and G12D are the most common mutated gene found in KRAS gene in codon 12 [50], accounting for 70% of all KRAS mutation [51].…”

“…Various studies have associated specific KRAS mutations with different likelihood of survival [49,51]. Bai et al (2017) determined that G12V and G12D have been associated with an increased risk of CRC associated death [50], while Jones et al (2017) established that G12C and G12V were predictors of worse OS [52]. Between G12D, G12S and G13D KRAS mutations, our study corroborates that mutant KRAS mCRC patients with G12D have the lowest survival median at 23 months (95% CI 15.4-34.6).…”