Wang Lei, Hu Haichuan, Pan Yunjian, Wang Rui, Li Yuan, Shen Lei, Yu Yongfu, Li Hang, Cai Deng, Sun Yihua, Chen Haiquan
Department of Thoracic Surgery, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China ; Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University Shanghai Cancer Center, Shanghai, China ; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
PLoS One. 2014 Feb 12;9(2):e88291. doi: 10.1371/journal.pone.0088291. eCollection 2014.
PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer. Here we investigated PIK3CA gene alterations, the expression of core components of PI3K pathway, and evaluated their clinical importance in non-small cell lung cancer (NSCLC).
Oncogenic mutations/rearrangements in PIK3CA, EGFR, KRAS, HER2, BRAF, AKT1 and ALK genes were detected in tumors from 1117 patients with NSCLC. PIK3CA gene copy number was examined by fluorescent in situ hybridization and the expression of PI3K p110 subunit alpha (PI3K p110α), p-Akt, mTOR, PTEN was determined by immunohistochemistry in PIK3CA mutant cases and 108 patients without PIK3CA mutation.
PIK3CA mutation was found in 3.9% of squamous cell carcinoma and 2.7% of adenocarcinoma. Among 34 PIK3CA mutant cases, 17 tumors harbored concurrent EGFR mutations and 4 had KRAS mutations. PIK3CA mutation was significantly associated with high expression of PI3K p110α (p<0.0001), p-Akt (p = 0.024) and mTOR (p = 0.001), but not correlated with PIK3CA amplification (p = 0.463). Patients with single PIK3CA mutation had shorter overall survival than those with PIK3CA-EGFR/KRAS co-mutation or wildtype PIK3CA (p = 0.004). A significantly worse survival was also found in patients with PIK3CA mutations than those without PIK3CA mutations in the EGFR/KRAS wildtype subgroup (p = 0.043).
PIK3CA mutations frequently coexist with EGFR/KRAS mutations. The poor prognosis of patients with single PIK3CA mutation in NSCLC and the prognostic value of PIK3CA mutation in EGFR/KRAS wildtype subgroup suggest the distinct mutation status of PIK3CA gene should be determined for individual therapeutic strategies in NSCLC.
编码磷脂酰肌醇-3-激酶（PI3K）催化亚基的PIK3CA基因在包括肺癌在内的多种肿瘤中发生突变和/或扩增。在此，我们研究了PIK3CA基因改变、PI3K通路核心成分的表达，并评估了它们在非小细胞肺癌（NSCLC）中的临床意义。
检测了1117例NSCLC患者肿瘤中PIK3CA、EGFR、KRAS、HER2、BRAF、AKT1和ALK基因的致癌突变/重排。通过荧光原位杂交检测PIK3CA基因拷贝数，并在PIK3CA突变病例和108例无PIK3CA突变的患者中通过免疫组织化学测定PI3K p110亚基α（PI3K p110α）、p-Akt、mTOR、PTEN的表达。
在3.9%的鳞状细胞癌和2.7%的腺癌中发现了PIK3CA突变。在34例PIK3CA突变病例中，17例肿瘤同时存在EGFR突变，4例有KRAS突变。PIK3CA突变与PI3K p110α（p<0.0001）、p-Akt（p = 0.024）和mTOR（p = 0.001）的高表达显著相关，但与PIK3CA扩增无关（p = 0.463）。单一PIK3CA突变的患者总生存期短于PIK3CA-EGFR/KRAS共突变或PIK3CA野生型的患者（p = 0.004）。在EGFR/KRAS野生型亚组中，PIK3CA突变的患者生存率也明显低于无PIK3CA突变的患者（p = 0.043）。
PIK3CA突变常与EGFR/KRAS突变共存。NSCLC中单一PIK3CA突变患者的不良预后以及PIK3CA突变在EGFR/KRAS野生型亚组中的预后价值表明，应确定PIK3CA基因的不同突变状态，以便为NSCLC的个体化治疗策略提供依据。
