Unveiling the role of KRAS in Chinese colorectal cancer patients: a positive influence on tumor mutational burden.

Abstract

Background: One of the main challenges associated with the development of therapeutic and diagnostic strategies for patients with colorectal cancer (CRC) is the establishment of minimally invasive and efficient biomarkers. Pertinent genes in CRC have been identified through their functions in systematic mutagenesis screens. KRAS is considered a dominant mutated oncogene that contributes to pathogenesis of CRC. This study aimed to explore the genomic alternations of KRAS in a CRC population.

Methods: Sequencing data of 94 Chinese patients with CRC were prospectively collected and analyzed using next-generation sequencing (NGS). The influence of KRAS and its associated subtype co-mutations on the expression level of the tumor mutational burden (TMB) was investigated. The objective of our study was to assess the potential prognostic significance of KRAS and other driving oncogenes in determining the clinical efficacy of immunotherapy.

Results: The gene mutation rates of TP53, APC, and KRAS were 81.91%, 71.28%, and 43.62%, respectively. Additionally, KRAS G12D displayed a relatively higher mutation rate than other KRAS-mutant subtypes. Increased TMB was observed in cases of KRAS and BRAF mutation combined with APC single mutation; furthermore, the expression of TMB in G12V was the highest, and G12D presented the lowest TMB in single KRAS-mutant subtypes or the combination with APC mutations.

Conclusions: The TMB driven by KRAS co-mutations may have the potential to be used as a key biomarker for prediction of treatment outcomes of immune checkpoint inhibitors (ICIs) in patients with CRC, especially with APC co-mutation.