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Prognostic Value of KRAS Mutation Subtypes and PD-L1 Expression in Patients With Lung Adenocarcinoma

克拉斯 医学 危险系数 内科学 腺癌 肿瘤科 肺癌 癌症 突变 队列 结直肠癌 基因 遗传学 生物 置信区间
作者
Luwei Tao,Ruoyu Miao,Tarek Mekhail,Jingxin Sun,Lingbin Meng,Cheng Fang,Jian Guan,Akriti G Jain,Yuan Du,Amanda Allen,Brenda L. Rzeszutko,Mark A. Socinski,Chung-Che Chang
出处
期刊:Clinical Lung Cancer [Elsevier]
卷期号:22 (4): e506-e511 被引量:8
标识
DOI:10.1016/j.cllc.2020.07.004
摘要

The prognostic value of different KRAS (Kirsten rat sarcoma viral oncogene) mutation subtypes and their association with programmed death ligand 1 (PD-L1) expression in lung adenocarcinoma (LADC) remain unclear. We examined the association of KRAS mutation subtypes with clinical outcomes and PD-L1 expression status.Patients diagnosed with KRAS-mutated LADC were evaluated for PD-L1 expression, cancer staging, overall survival (OS), and relapse-free survival.A cohort of 254 KRAS-mutated LADC patients (median follow-up, 17 months) was studied. The 3 major subtypes of KRAS mutations were G12C (46.1%), G12V (21.7%), and G12D (15.7%). We found that all these subtypes had no impact on cancer stages, brain metastasis at diagnosis, OS, and relapse-free survival. Among this cohort, 33% of 94 patients who had PD-L1 staining data available had PD-L1-positive disease (≥ 1% of tumor cells). PD-L1 expression status was not significantly different among the 3 major mutation subtypes. Of interest, among patients with G12C mutation, positive PD-L1 expression was associated with significantly shorter OS (median survival, 5.7 vs. 12.8 months, P = .007). In multivariable analysis, PD-L1 positivity remained as an adverse factor for OS, with hazard ratio of 4.44 (P = .0007). PD-L1 status did not affect OS in other subtypes of mutations.KRAS mutation subtype is not associated with patient clinical outcomes or PD-L1 expression status. However, PD-L1 positivity appears to negatively affect OS in LADC patients with G12C mutation. Further study is needed to confirm our observation and to determine if programmed cell death 1/PD-L1 antagonist may affect the clinical outcome of patients with different KRAS mutation subtypes.
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