Gow Chien-Hung, Hsieh Min-Shu, Chen Yi-Lin, Liu Yi-Nan, Wu Shang-Gin, Shih Jin-Yuan
Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.
Front Oncol. 2023 Mar 9;13:1113696. doi: 10.3389/fonc.2023.1113696. eCollection 2023.
The exon 14 skipping ex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the ex14 mutation to analyze their survival outcomes and associated prognostic factors.
A one-step reverse transcription-polymerase chain reaction to examine the presence of the ex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected and mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with ex14-positive tumors.
ex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the ex14 mutation, lung cancer patients harboring the ex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of ex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the ex14 mutations showed similarly poor overall survival (OS) ( = 0.429). For all 36 ex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining ( = 0.006), initial brain metastasis ( = 0.005), and administration of only supportive care ( < 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with ex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment ( = 0.003), lung radiotherapy ( = 0.020), initial brain metastasis ( = 0.005), and strong c-MET IHC staining ( = 0.012) were independent prognostic factors for OS in these patients.
A higher frequency of ex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the mutations had similarly poor overall survival. Pemetrexed-based chemotherapy, strong c-MET ICH staining, initial brain metastasis, and lung radiotherapy, may help predict survival outcomes in patients with advanced lung ADCs harboring the ex14 mutation.
外显子14跳跃（ex14）突变是肺癌中一种重要的致癌驱动因素。我们对患有ex14突变的肺癌患者的临床数据进行了回顾性分析，以分析他们的生存结果和相关预后因素。
使用来自1374例未检测到 和 突变的肺癌患者的RNA样本，进行一步逆转录-聚合酶链反应以检测ex14突变的存在。对ex14阳性肿瘤患者的病理特征和c-MET免疫组织化学（IHC）结果进行分析。
在69例肺癌患者中鉴定出ex14，其中包括53例腺癌（ADC）和16例非ADC患者。与没有ex14突变的患者相比，携带ex14突变的肺癌患者通常为老年人、从不吸烟者，且体能状态评分较差。在肺肉瘤样癌（PSC）患者中检测到更高频率的ex14突变（24.3%，n = 9/37）。然而，有或没有ex14突变的IV期PSC患者的总生存期（OS）同样较差（ = 0.429）。对于所有36例ex14阳性肺ADC，多因素分析显示了几个不良预后因素，包括c-MET IHC强染色（ = 0.006）、初始脑转移（ = 0.005）和仅接受支持性治疗（ < 0.001）。在排除7例仅接受支持性治疗的患者后，我们进一步分析了29例接受抗癌治疗的IV期ex14突变肺ADC患者。多因素分析显示培美曲塞治疗（ = 0.003）、肺部放疗（ = 0.020）、初始脑转移（ = 0.005）和c-MET IHC强染色（ = 0.012）是这些患者OS的独立预后因素。
在PSC患者中检测到更高频率的ex14突变。有或没有 突变的IV期PSC患者的总生存期同样较差。基于培美曲塞的化疗、c-MET ICH强染色、初始脑转移和肺部放疗，可能有助于预测携带ex14突变的晚期肺ADC患者的生存结果。
