Pan-cancer analysis to character the clinicopathological and genomic features of KRAS-mutated patients in China.

Abstract

Purpose: The Kirsten rat sarcoma viral oncogene (KRAS) is the most frequently mutated oncogene in human cancers. Significant advancements have been made in targeted therapy and immunotherapy for this gene in recent years, underscoring the importance of comprehensively understanding the genomic landscape of KRAS across various cancer types.

Methods: Using next-generation sequencing (NGS) technology and a panel of 520 genes, KRAS mutations, tumor mutation burden (TMB), and microsatellite instability (MSI-H) status were investigated.

Results: An analysis of 10,820 tumor samples found KRAS mutations in 19.97% of cases. Pancreatic cancer showed the highest prevalence of KRAS mutations at 73.51%, while colorectal at 41.45%, uterine at 21.23%, and lung cancer at 11.24%. KRAS G12D mutation is most common in pancreatic, colorectal, and gastric cancers, while KRAS G12V mutation is predominant in uterine cancer, and KRAS G12C mutation is most frequent in lung cancer. Significant correlations were found between TMB and KRAS G13D/G12V mutations in colorectal cancer. KRAS G13D notably affected TMB in uterus cancer, while KRAS G12C mutation was linked to high TMB in lung cancer. Moreover, statistical analysis revealed a significant association between KRAS G13D/G12V mutations and MSI-H in colorectal cancer.

Conclusions: KRAS mutations were most frequent in cancers of the digestive, female reproductive, and respiratory systems. Specific KRAS mutations are associated with TMB and MSI in various cancer types.