Abstract 762: Clinical characteristics and prognostic value of the KRASmutation in Chinese colorectal cancer patients

Background: The KRAS mutation are high-frequency somatic mutations found in the colorectal cancer (CRC) patients both from Western and Asian countries, but except for exon 2 of KRAS, other prevalence and prognostic value have not been adequately assessed in Asian patients. The aim of this study was to determine the mutation frequencies of whole exon mutation of KRAS in Chinese CRC patients and to investigate their impact on prognosis. Methods: 7189 tumor tissue samples (iCohort) were subjected to next-generation sequencing (NGS) for detection the KRAS mutation. All pathologic or likely pathologic mutations of KRAS were considered. In addition, clinical features and prognostic dates were collected from 145 patients at the third affliated Hospital of Soochow University (sCohort) and used ddPCR to detect KRAS mutations. Results: In the iCohort, 2706 patients (37.6%) were confirmed harboring KRAS mutation. The most frequent mutations in KRAS were G12D (32.19%), G12V (17.96%) and G13D (17.59%). In the sCohort, 51 CRC patients (35.17%) had KRAS mutations, among which KRAS G12D (64.71%), G13D (29.41%) and G14D (3.92%) were high-frequency mutations. The KRAS mutation was associated with shorter median overall survival (OS) than wild-type tumors (mOS, 69 vs 55 months; HR, 1.80; 95% Cl 1.22-2.64; P=0.0003). In Cox multivariate analysis, age (HR, 1.562; 95% Cl 1.10-2.22; P=0.013), tumor differentiation (HR, 0.417; 95% Cl 0.19-0.90; P=0.026) and KRAS mutation (HR, 1.897; 95% Cl 0.19-0.90; P=0.001) remained independent predictor of shorter OS. Among the common KRAS mutations, G12D was significantly associated with shorter OS (HR, 2.17; 95% Cl 1.31-3.58; P Conclusions: Our findings indicate that KRAS genes are frequently mutated and over 30% harbored the KRAS G12D mutation subtype. Our finding that KRAS G12D mutation is associated with inferior survival and a biomarker of poor prognosis in Chinese patients. Our data emphasizes the importance of molecular features in CRC patients, which could potentially be improved by G12D-specific related inhibitors. Citation Format: Ye Yuan, Wei Wang, Jiemin Zhao, Junling Zhang, Shiqing Chen, Chunti Shen, Changping Wu, Wenwei Hu. Clinical characteristics and prognostic value of the KRASmutation in Chinese colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 762.