KRAS G12C突变的非小细胞肺癌患者的基因突变谱及临床病理学特征的单中心回顾性研究

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation:a single-center retrospective study

目的为了精准地筛选出携带KRAS G12C突变的非小细胞肺癌(NSCLC)患者,并评估其临床病理学特征、预后影响因素及目前的治疗现状。方法回顾性筛查上海市胸科医院病理科2018年1月至2021年9月的19410例NSCLC标本,筛选经二代测序检测为KRAS基因突变的病例,收集并分析这些病例的临床病理学特征和基因突变数据。结果共1633例(8.4%)NSCLC病例携带KRAS基因突变,其中G12C(468例,28.7%)是最主要的突变亚型;该突变更常见于男性(414/468,88.5%)、有吸烟史(308/468,65.8%)、病理类型为肺浸润性腺癌(231/468,49.4%)的患者。KRAS G12C突变型NSCLC最常见的共突变基因包括:TP53(52.4%,245/468)、STK11(18.6%,87/468)和ATM(13.2%,62/468)。KRAS G12C突变型NSCLC相较于非G12C突变患者,PD-L1表达(≥1%)的比例显著升高[64.3%(90/140)比56.1%(193/344),P=0.014],且接受免疫检查点抑制剂(ICI)治疗能显著延长NSCLC患者的无进展生存期(PFS;10.0个月比5.0个月,P=0.011)。在化疗和ICI治疗的基础上联合抗血管抑制剂或多靶点抑制剂并不能显著提高KRAS G12C突变型NSCLC患者的PFS(P>0.05)。接受ICI治疗的KRAS G12C突变型NSCLC患者,携带TP53突变的KRAS G12C患者,与携带STK11突变的KRAS G12C患者相比,其中位PFS显著延长(9.0个月比4.3个月,P=0.012)。结论KRAS G12C突变型NSCLC患者的PD-L1表达水平相对更高,且能从ICI治疗中获益;化疗、ICI治疗及其联合用药的可行性还有待进一步探究。

Objective To accurately screen non-small cell lung cancer(NSCLC)patients with KRAS G12C mutation and to evaluate their clinicopathological features,prognostic factors and current treatment status.Methods A total of 19410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital,Shanghai,China from January 2018 to September 2021 were retrospectively reviewed,and the cases with KRAS gene mutation detected by next-generation sequencing were included.The clinicopathological and genetic mutation data of these cases were collected and analyzed.Results A total of 1633(8.4%)NSCLC patients carried a KRAS gene mutation,among whom G12C was the most frequent(468 cases,28.7%)mutant subtype.The mutation was more commonly found in males(414/468,88.5%),patients with a history of smoking(308/468,65.8%),and patients with a pathological type of invasive adenocarcinoma(231/468,49.4%).The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53(52.4%,245/468),STK11(18.6%,87/468)and ATM(13.2%,62/468).The proportion of PD-L1 expression(≥1%)in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation[64.3%(90/140)vs.56.1%(193/344),P=0.014].Immune checkpoint inhibitors(ICIs)treatment significantly prolonged progression-free survival(PFS)in NSCLC patients(10.0 months vs.5.0 months,P=0.011).However,combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC(P>0.05).Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation(9.0 months vs.4.3 months,P=0.012).Conclusions Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment.The feasibility of chemotherapy,ICIs therapy and their combination needs further investigation.