Department of Pulmonary Medicine, Affiliated Cancer Hospital of Xinjiang Medical University, No. 789 Suzhou East Street, Xincheng District, Urumqi, Xinjiang, 830011, China.
Education and Research Management Office, Affiliated Cancer Hospital of Xinjiang Medical University, No. 789 Suzhou East Street, Xincheng District, Urumqi, Xinjiang, 830011, China.
J Cancer Res Clin Oncol. 2024 Sep 7;150(9):413. doi: 10.1007/s00432-024-05932-x.
Non-small cell lung cancer (NSCLC) is a highly fatal malignancy. The Kirsten rat sarcoma viral oncogene (KRAS) gene profoundly impacts patient prognosis. This study aims to explore the correlation between KRAS mutation subtypes, clinical data, and the impact of these subtypes on immunotherapy.
Tumor samples from 269 NSCLC patients at the Affiliated Cancer Hospital of Xinjiang Medical University were analyzed. Patients received first- or second-line therapy without targeted therapy. Molecular and clinical data were used to analysis KRAS mutation subtypes and treatment outcomes.
KRAS mutations predominantly included G12C, G12D, and G12V subtypes. TP53 had the highest mutation frequency among KRAS mutations, followed by MST1, STK11, and KMT2C. Gender differences were noted among KRAS mutation subtypes, with G12C and G12V mutations prevalent in males, while G12D mutations were less common among males. Smokers exhibited varied KRAS mutation subtypes, with G12C and G12V prevalent in smokers and G12D in nonsmokers. KRAS mutations were mainly in lung adenocarcinoma. TTF-1 and PD-L1 expression differed significantly among KRAS mutations. Patients with G12C and G12V mutations showed higher TMB levels and better immunotherapy outcomes compared to those without KRAS mutations. Conversely, patients with G12D mutations had poorer immunotherapy responses.
KRAS mutation subtypes exhibit distinct clinical and molecular characteristics and varying responses to immunotherapy. G12C and G12V mutations correlate with better immunotherapy outcomes, while G12D mutations are associated with poorer responses.
非小细胞肺癌（NSCLC）是一种高度致命的恶性肿瘤。Kirsten 大鼠肉瘤病毒癌基因（KRAS）基因对患者预后有深远影响。本研究旨在探讨 KRAS 突变亚型与临床数据的相关性，以及这些亚型对免疫治疗的影响。
对新疆医科大学附属肿瘤医院 269 例 NSCLC 患者的肿瘤样本进行分析。患者在未接受靶向治疗的情况下接受一线或二线治疗。利用分子和临床数据分析 KRAS 突变亚型和治疗结果。
KRAS 突变主要包括 G12C、G12D 和 G12V 亚型。在 KRAS 突变中，TP53 的突变频率最高，其次是 MST1、STK11 和 KMT2C。KRAS 突变亚型存在性别差异，G12C 和 G12V 突变多见于男性，而 G12D 突变在男性中较少见。吸烟者的 KRAS 突变亚型存在差异，G12C 和 G12V 突变多见于吸烟者，而 G12D 突变多见于不吸烟者。KRAS 突变主要发生在肺腺癌中。KRAS 突变与 TTF-1 和 PD-L1 的表达存在显著差异。与无 KRAS 突变的患者相比，携带 G12C 和 G12V 突变的患者 TMB 水平更高，免疫治疗效果更好。相反，携带 G12D 突变的患者免疫治疗反应较差。
KRAS 突变亚型表现出不同的临床和分子特征，对免疫治疗的反应也不同。G12C 和 G12V 突变与更好的免疫治疗效果相关，而 G12D 突变与较差的免疫治疗反应相关。
