Cancer：基因KRAS突变与晚期肺腺癌患者更短存活相关联

根据一项于2012年7月18日在线发表在Cancer期刊上的研究，就晚期肺腺癌患者而言，基因KRAS突变就能够预测更短的存活时间。来自美国西北大学的Melissa L. Johnson博士和同事们在2002年到2009年期间评价了1036名晚期肺腺癌患者(59%为女性；33%为从没有吸过烟的人)体内的基因EGFR和KRAS的突变状态，并利用这些数据研究了KRAS突变的预后意义。

研究人员发现这些患者的平均年龄为65岁，而且他们当中81%的卡氏行为表现状态(Karnofsky performance status)分数为80或者更高。在多变量分析之后，研究人员还发现，EGFR突变与更长的总生存期(风险比为0.60；P<0.001)相关联，而KRAS突变与更短的存活时间(风险比为1.21; P=0.048)相关联。

研究人员写道，“总之，我们报道，KRAS突变的存在是肺腺癌患者的一个不良预后因素。鉴于携带KRAS突变的患者通常接受一种导致他们存活时间更短的临床治疗方案，因此他们应当在临床试验中单独地接受评估。我们建议在前期突变分析中应当将KRAS检测与EGFR突变和EML4-ALK突变检测一起进行以便能够在诊所鉴定出这些病人。”

本文编译自KRAS mutations predict shorter survival in lung cancer

doi: 10.1002/cncr.27730
PMC:
PMID:

Association of KRAS and EGFR mutations with survival in patients with advanced lung adenocarcinomas

Melissa L. Johnson MD1,†,*, Camelia S. Sima MD2, Jamie Chaft MD3, Paul K. Paik MD3, William Pao MD6, Mark G. Kris MD3,5, Marc Ladanyi MD4, Gregory J. Riely MD

BACKGROUND: Lung adenocarcinomas can be distinguished by identifying mutated driver oncogenes, including epidermal growth factor receptor (EGFR) and KRAS. Mutations in EGFR are associated with both improved survival as well as response to treatment with erlotinib and gefitinib. However, the prognostic significance of KRAS has not been evaluated in large numbers of patients and remains controversial. For the current report, the authors examined the association of EGFR and KRAS mutations with survival among patients with advanced lung adenocarcinomas. METHODS: Data were analyzed from patients with advanced lung adenocarcinomas who had known EGFR and KRAS mutation status evaluated between 2002 and 2009. The collected clinical variables included age, sex, Karnofsky performance status, smoking history, and treatment history. Overall survival from the diagnosis of advanced disease was analyzed using Kaplan-Meier and Cox proportional hazard methods. RESULTS: In total, 1036 patients were evaluated, including 610 women (59%) and 344 never-smokers (33%). The median patient age was 65 years (range, 25-92 years), and the majority of patients (81%) had a Karnofsky performance status ≥80%. In multivariate analysis, EGFR mutations were associated with longer overall survival (hazard ratio, 0.6; P < .001), and KRAS mutations were associated with shorter survival (hazard ratio, 1.21; P = .048). CONCLUSIONS: KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinomas. The presence of EGFR and KRAS mutations define distinct subsets of patients with lung adenocarcinomas and should be determined in patients when they are diagnosed with advanced disease. Clinical trial reports should include EGFR and KRAS mutation status along with other prognostic factors. Cancer 2012. © 2012 American Cancer Society.