临床与病理杂志2025，Vol.45Issue(7)：787-797,11.DOI:10.11817/j.issn.2095-6959.2025.250281
结直肠癌KRAS突变亚型的临床病理特征
Clinicopathological characteristics of KRAS mutation subtypes in colorectal cancer
摘要
Abstract
Objective:The KRAS gene,a key regulatory factor in the rat sarcoma(RAS)/mitogen-activated protein kinase(MAPK)signaling pathway,represents one of the most critical molecular events in colorectal cancer(CRC).However,different KRAS mutation subtypes may exhibit significant clinical heterogeneity.This study aims to investigate the clinicopathological characteristics of various KRAS mutation subtypes in CRC. Methods:A retrospective analysis was conducted on 164 surgical specimens of CRC collected at the First Affiliated Hospital of Soochow University between January 2019 and December 2024.Expression levels of mismatch repair proteins[mutL homolog 1(MLH1),postmeiotic segregation increased 2(PMS2),mutS homolog(MSH)2,MSH6],amplification status of human epidermal growth factor receptor 2(HER2),and Ki-67 expression were obtained.KRAS mutation subtypes were identified using quantitative fluorescence PCR.In addition,KRAS mutation and prognostic data for CRC were downloaded from the Cancer Genome Atlas database,and survival outcomes were compared across mutation subtypes. Results:The KRAS mutation rate in CRC was 52.44%,predominantly involving exon 2,with high-frequency mutations at G12D,G12V,and G13D.The proportion of right-sided colon cancer was significantly higher in the KRAS-mutant group than in the wild-type group(P<0.001).Subtype analysis revealed that the G13D subtype was significantly associated with MSH6 loss(P=0.021),while G12A mutations were frequently accompanied by distant metastasis.The proportion of cases with high proliferative activity(Ki-67 proliferation index>70%)was significantly higher in G12D than in G12V mutations(P=0.038),and the G12C subtype also showed a high-proliferation profile.Prognostic analysis based on TCGA data indicated that the exon 3 Q61L/R/H and exon 2 G12C subtypes were associated with poorer outcomes. Conclusion:Distinct KRAS mutation subtypes in colorectal cancer display notable clinical heterogeneity.KRAS genotyping can thus provide valuable guidance for personalized therapeutic decision-making in CRC.关键词
结直肠癌/KRAS/临床病理特征/基因突变/突变亚型Key words
colorectal cancer/KRAS/clinicopathological characteristics/gene mutation/mutation subtype引用本文复制引用
阎萌,张昊,李三恩,郭凌川..结直肠癌KRAS突变亚型的临床病理特征[J].临床与病理杂志,2025,45(7):787-797,11.基金项目
苏州市"科教兴卫"青年科技项目(KJXW2022008) （KJXW2022008）
吴阶平医学基金会临床科研专项资助基金(320.6750.2024-24-10).This work was supported by the Suzhou"Ke Jiao Xing Wei"Youth Science and Technology Project(KJXW2022008)and the Wu Jieping Medical Foundation Special Fund for Clinical Research(320.6750.2024-24-10),China. （320.6750.2024-24-10）
