Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France; INSERM U981, Gustave Roussy Cancer Campus, Villejuif, France; Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, France.
Lung Cancer. 2017 Oct;112:62-68. doi: 10.1016/j.lungcan.2017.08.002. Epub 2017 Aug 7.
LKB1/STK11 (STK11) is among the most inactivated tumor-suppressor genes in non-small cell lung cancer (NSCLC). While evidence concerning the biologic role of STK11 is accumulating, its prognostic significance in advanced NSCLC has not been envisaged yet.
This retrospective analysis included consecutive NSCLC patients with available STK11 information who underwent a platinum-based chemotherapy. STK11 mutational status was correlated to clinico-pathological and mutational features. Kaplan-Meier and Cox models were used for survival curves and multivariate analyses, respectively.
Among the 302 patients included, 267 (89%) were diagnosed with stage IIIB/IV NSCLC and 25 (8%) harbored a STK11 mutation (STK11mut). No statistical differences were observed between STK11 status and clinico-pathological variables. We detected a significant correlation between STK11 and KRAS status (p=0.008); among the 25 STK11mut patients, 13 (52%) harbored a concomitant KRAS mutation. Overall survival (OS) was shorter for STK11mut (median OS=10.4months) compared to wild-type patients (STK11wt; median OS=17.3months) in univariate analysis (p=0.085). STK11 status did not impact upon OS in multivariate analysis (p=0.45) and non-significant results were observed for progression-free survival. The co-occurrence of KRAS and STK11 mutations suggest a trend toward detrimental effect in OS (p=0.12).
In our cohort enriched for advanced NSCLC patients who received platinum-based chemotherapy, STK11 mutations were not specifically associated with clinico-pathological features and they did not impact upon survival. We confirm the positive correlation between STK11 and KRAS mutations. The co-occurrence of KRAS and STK11 mutations could label a more aggressive molecular subtype of NSCLC.
LKB1/STK11（STK11）是在非小细胞肺癌（NSCLC）中失活最多的肿瘤抑制基因之一。虽然关于 STK11 的生物学作用的证据正在积累，但它在晚期 NSCLC 中的预后意义尚未被设想。
本回顾性分析包括了接受铂类化疗的连续 NSCLC 患者，他们有可用的 STK11 信息。STK11 突变状态与临床病理和突变特征相关联。Kaplan-Meier 和 Cox 模型分别用于生存曲线和多变量分析。
在包括的 302 名患者中，267 名（89%）被诊断为 IIIB/IV 期 NSCLC，25 名（8%）携带 STK11 突变（STK11mut）。STK11 状态与临床病理变量之间没有观察到统计学差异。我们检测到 STK11 与 KRAS 状态之间存在显著相关性（p=0.008）；在 25 名 STK11mut 患者中，有 13 名（52%）同时携带 KRAS 突变。单变量分析中，STK11mut 患者的总生存期（OS）较短（中位 OS=10.4 个月），而野生型患者（STK11wt；中位 OS=17.3 个月）（p=0.085）。多变量分析中 STK11 状态对 OS 没有影响（p=0.45），无进展生存期也无显著结果。KRAS 和 STK11 突变的共存提示 OS 有不利影响的趋势（p=0.12）。
在我们的队列中，晚期 NSCLC 患者接受铂类化疗，STK11 突变与临床病理特征无特异性相关，且不影响生存。我们证实了 STK11 与 KRAS 突变之间的正相关。KRAS 和 STK11 突变的共存可能标记了 NSCLC 的一种更具侵袭性的分子亚型。
