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完全切除的肺腺癌患者中PIK3CA的突变及预后分析

Mutation and prognostic analyses of PIK3CA in patients with completely resected lung adenocarcinoma.

作者信息

Song Zhengbo, Yu Xinmin, Zhang Yiping

机构信息

Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, 310022, China.

Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang, 310022, China.

出版信息

Cancer Med. 2016 Oct;5(10):2694-2700. doi: 10.1002/cam4.852. Epub 2016 Aug 23.

Abstract

PIK3CA mutation represents a clinical subset of diverse carcinomas. We explored the status of PIK3CA mutation and evaluated its genetic variability, treatment, and prognosis in patients with lung adenocarcinoma. A total of 810 patients with completely resected lung adenocarcinoma were recruited between 2008 and 2013. The status of PIK3CA mutation and other three genes, that is, EGFR mutation, KRAS mutation and ALK fusion were examined by reverse transcription-polymerase chain reaction (RT-PCR). Survival curves were plotted with the Kaplan-Meier method and log-rank for comparison. Cox proportional hazard model was performed for multivariate analysis. Among the 810 patients, 23 cases of PIK3CA mutation were identified with a frequency of 2.8%. There were 14 men and 9 women with a median age of 61 years. Seventeen tumors revealed concurrent gene abnormalities of EGFR mutation (n = 12), KRAS mutation (n = 3), and ALK fusion (n = 2). Seven patients with EGFR & PIK3CA mutations recurred and administrated of EGFR-TKIs yielded a median progression free-survival of 6.0 months. Among four eviromous-treated patients, stable disease was observed in three patients with a median Progression-free survival (PFS) of 3.5 months. Patients with and without PIK3CA mutation had different overall survivals (32.2 vs. 49.6 months, P = 0.003). Multivariate analysis revealed that PIK3CA mutation was an independent predictor of poor overall survival (HR = 2.37, P = 0.017). The frequency of PIK3CA mutation was around 2.8% in the Chinese patients of lung adenocarcinoma. PIK3CA mutation was associated with reduced PFS of EGFR-TKIs treatment and shorter overall survival.

摘要

PIK3CA突变代表了多种癌症的一个临床亚组。我们探讨了PIK3CA突变状态,并评估了其在肺腺癌患者中的基因变异性、治疗及预后情况。2008年至2013年期间共招募了810例接受了肺腺癌完全切除术的患者。采用逆转录聚合酶链反应(RT-PCR)检测PIK3CA突变状态以及其他三个基因,即表皮生长因子受体(EGFR)突变、 Kirsten大鼠肉瘤病毒癌基因(KRAS)突变和间变性淋巴瘤激酶(ALK)融合情况。采用Kaplan-Meier法绘制生存曲线并进行对数秩检验比较。采用Cox比例风险模型进行多因素分析。在810例患者中,共识别出23例PIK3CA突变,频率为2.8%。其中男性14例,女性9例,中位年龄为61岁。17例肿瘤显示同时存在EGFR突变(n = 12)、KRAS突变(n = 3)和ALK融合(n = 2)等基因异常。7例EGFR与PIK3CA突变患者出现复发,接受表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)治疗后的中位无进展生存期为6.0个月。在4例接受环境治疗的患者中,3例患者病情稳定,中位无进展生存期(PFS)为3.5个月。有和没有PIK3CA突变的患者总生存期不同(32.2个月对49.6个月,P = 0.003)。多因素分析显示,PIK3CA突变是总生存期较差的独立预测因素(风险比[HR]=2.37,P = 0.017)。在中国肺腺癌患者中,PIK3CA突变频率约为2.8%。PIK3CA突变与EGFR-TKIs治疗的无进展生存期缩短及总生存期缩短相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b05/5083721/5bc5c76f5de1/CAM4-5-2694-g001.jpg

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