Zhang YuXuan, Shen Yuhong, Wu Jiayuan, Zhang Jun, Cao Chenxi, Mo Juanfen, Bao Yi
The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310000, People's Republic of China.
The Key Laboratory, the Second Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People's Republic of China.
Onco Targets Ther. 2024 Sep 11;17:755-763. doi: 10.2147/OTT.S468352. eCollection 2024.
PIK3CA-mutant non-small-cell lung cancer (NSCLC) is associated with other genetic mutations and may influence treatment strategies and clinical outcomes. We aimed to characterize PIK3CA mutations co-occurring with several major driver mutations using data from published cohorts and our medical center.
We analyzed NSCLC patients harboring PIK3CA mutations from The Cancer Genome Atlas (TCGA) and Memorial Sloan Kettering (MSK) databases and retrospectively identified NSCLC patients with PIK3CA-mutants at a single medical center from our electronic records. The Log rank test was used to determine the association between PIK3CA mutations and overall survival (OS) in NSCLC patients.
Common hotspot mutations in PIK3CA were found in exon 9 (c.1633G > A, E545K, and c.1624G > A, E542K) and exon 20 (c.3140A > G, H1047R) in all cohorts. Co-occurring mutations of PIK3CA with EGFR, KRAS, and TP53 have been frequently observed in patients with NSCLC, with different percentages in these datasets generated by different background. PIK3CA mutations were observed to be significantly associated with poor OS in lung adenocarcinomas patients in the MSKCC cohort (hazard ratio [HR] = 0.519, 95% confidence interval [CI] = 0.301-0.896; <0.05).
PIK3CA co-occurring mutations in other genes may represent distinct subsets of NSCLC. Further elucidation of the roles of PIK3CA hotspot mutations combined with other driver mutations, including EGFR and KRAS, is needed to guide effective treatment in patients with advanced NSCLC.
磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）突变的非小细胞肺癌（NSCLC）与其他基因突变相关，可能影响治疗策略和临床结局。我们旨在利用已发表队列和我们医疗中心的数据，对与几种主要驱动基因突变同时发生的PIK3CA突变进行特征分析。
我们分析了来自癌症基因组图谱（TCGA）和纪念斯隆凯特琳癌症中心（MSK）数据库中携带PIK3CA突变的NSCLC患者，并从我们的电子记录中回顾性鉴定了单个医疗中心的PIK3CA突变NSCLC患者。采用对数秩检验确定NSCLC患者中PIK3CA突变与总生存期（OS）之间的关联。
在所有队列中，PIK3CA的常见热点突变见于第9外显子（c.1633G＞A，E545K和c.1624G＞A，E542K）和第20外显子（c.3140A＞G，H1047R）。在NSCLC患者中经常观察到PIK3CA与表皮生长因子受体（EGFR）、 Kirsten大鼠肉瘤病毒癌基因（KRAS）和肿瘤蛋白p53（TP53）同时发生突变，在不同背景产生的这些数据集中比例不同。在MSKCC队列的肺腺癌患者中，观察到PIK3CA突变与较差的OS显著相关（风险比[HR]=0.519，95%置信区间[CI]=0.301-0.896；P＜0.05）。
PIK3CA与其他基因同时发生的突变可能代表NSCLC的不同亚组。需要进一步阐明PIK3CA热点突变与包括EGFR和KRAS在内的其他驱动基因突变联合的作用，以指导晚期NSCLC患者的有效治疗。
