Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes.
Impact of KRAS mutation subtype and concurrent pathogenic mutations on non-small cell lung cancer outcomes.
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DOI：
10.1016/j.lungcan.2019.05.015
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发表时间：
2019-07
期刊：
影响因子：
5.3
通讯作者：
Wakelee, Heather A.
中科院分区：
文献类型：
--
作者：
Aredo, Jacqueline, V;Padda, Sukhmani K.;Kunder, Christian A.;Han, Summer S.;Neal, Joel W.;Shrager, Joseph B.;Wakelee, Heather A.
KRAS 突变的非小细胞肺癌 (NSCLC) 中普遍存在并发基因突变，可能对患者的预后产生不同的影响。我们试图表征 KRAS 突变亚型和并发致病性突变对总生存期 (OS) 和 PD-L1 表达（抗 PD-1/PD-L1 免疫治疗的预测生物标志物）的影响。我们回顾性地鉴定了单个机构中患有 KRAS 突变的 NSCLC 患者，并从电子健康记录中提取了临床、分子和病理数据。 Cox 回归和多项 Logistic 回归用于确定 KRAS 突变亚型和并发致病性突变分别与 OS 和肿瘤 PD-L1 表达的关系。总共包括 186 名患者。常见的 KRAS 突变亚型包括 G12C (35%) 和 G12D (17%)。在 TP53 (39%)、STK11 (12%)、KEAP1 (8%) 和 PIK3CA (4%) 中发现了并发致病突变。在多变量分析中，KRAS G12D 突变与较差的 OS 显着相关（风险比 [HR] 2.43，95% 置信区间 [CI] 1.15–5.16；P = 0.021），STK11 共突变也是如此（HR 2.95，95% CI 1.27–6.88；P = 0.012）。与无 (< 1%) PD-L1 表达相比，KRAS G12C 突变与阳性但低 (1–49%) PD-L1 表达显着相关（优势比 [OR] 4.94，95% CI 1.07–22.85；P =0.041），TP53 共突变与高 (≥50%) PD-L1 表达显着相关（OR 6.36，95% CI 1.84–22.02； P = 0.004）。 KRAS G12D 和 STK11 突变导致 KRAS 突变 NSCLC 患者预后不良。 KRAS G12C 和 TP53 突变与预测免疫治疗获益的生物标志物相关。并发突变可能代表 KRAS 突变 NSCLC 的不同子集；需要进一步研究以阐明它们在指导治疗中的作用。
Concurrent genetic mutations are prevalent in KRAS-mutant non-small cell lung cancer (NSCLC) and may differentially influence patient outcomes. We sought to characterize the effects of KRAS mutation subtypes and concurrent pathogenic mutations on overall survival (OS) and PD-L1 expression, a predictive biomarker for anti-PD-1/PD-L1 immunotherapy. We retrospectively identified patients with KRAS-mutant NSCLC at a single institution and abstracted clinical, molecular, and pathologic data from electronic health records. Cox regression and multinomial logistic regression were used to determine how KRAS mutation subtypes and concurrent pathogenic mutations are associated with OS and tumor PD-L1 expression, respectively. A total 186 patients were included. Common KRAS mutation subtypes included G12C (35%) and G12D (17%). Concurrent pathogenic mutations were identified in TP53 (39%), STK11 (12%), KEAP1 (8%), and PIK3CA (4%). On multivariable analysis, KRAS G12D mutations were significantly associated with poor OS (hazard ratio [HR] 2.43, 95% confidence interval [CI] 1.15–5.16; P = 0.021), as were STK11 co-mutations (HR 2.95, 95% CI 1.27–6.88; P = 0.012). Compared to no (< 1%) PD-L1 expression, KRAS G12C mutations were significantly associated with positive yet low (1–49%) PD-L1 expression (odds ratio [OR] 4.94, 95% CI 1.07–22.85; P =0.041), and TP53 co-mutations with high (≥50%) PD-L1 expression (OR 6.36, 95% CI 1.84–22.02; P = 0.004). KRAS G12D and STK11 mutations confer poor prognoses for patients with KRAS-mutant NSCLC. KRAS G12C and TP53 mutations correlate with a biomarker that predicts benefit from immunotherapy. Concurrent mutations may represent distinct subsets of KRAS-mutant NSCLC; further investigation is warranted to elucidate their role in guiding treatment.
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影响因子：
1.2
作者：
Gu J;Zhou Y;Huang L;Ou W;Wu J;Li S;Xu J;Feng J;Liu B
通讯作者：
Liu B
同时发生的基因组改变对KRAS突变非小细胞肺癌患者结局的影响。
DOI：
10.1158/1078-0432.ccr-17-1841
发表时间：
2018-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Arbour KC;Jordan E;Kim HR;Dienstag J;Yu HA;Sanchez-Vega F;Lito P;Berger M;Solit DB;Hellmann M;Kris MG;Rudin CM;Ni A;Arcila M;Ladanyi M;Riely GJ
通讯作者：
Riely GJ
KRAS 突变是 NSCLC 不良预后和治疗结果的弱但有效的预测因子：41 项研究的荟萃分析
影响因子：
--
作者：
Pan W;Yang Y;Zhu H;Zhang Y;Zhou R;Sun X
通讯作者：
Sun X
DOI：
10.1038/nrc3106
发表时间：
2011-10-13
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
5.3
作者：
Falk, Alexander T.;Yazbeck, Nathalie;Ilie, Marius
通讯作者：
Ilie, Marius