AUTHOR=Gow Chien-Hung , Hsieh Min-Shu , Chen Yi-Lin , Liu Yi-Nan , Wu Shang-Gin , Shih Jin-Yuan 

TITLE=Survival outcomes and prognostic factors of lung cancer patients with the MET exon 14 skipping mutation: A single-center real-world study

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1113696

DOI=10.3389/fonc.2023.1113696

ISSN=2234-943X

ABSTRACT=<sec><title>Introduction</title><p>The <italic>MET</italic> exon 14 skipping <italic>(MET</italic>ex14) mutation is an important oncogenic driver in lung cancer. We performed a retrospective analysis of clinical data from lung cancer patients with the <italic>MET</italic>ex14 mutation to analyze their survival outcomes and associated prognostic factors.</p></sec><sec><title>Methods</title><p>A one-step reverse transcription-polymerase chain reaction to examine the presence of the <italic>MET</italic>ex14 mutation was performed using RNA samples from 1374 lung cancer patients with no detected <italic>EGFR</italic> and <italic>ALK</italic> mutations. Pathological features and immunohistochemistry (IHC) results for c-MET were analyzed in patients with <italic>MET</italic>ex14-positive tumors.</p></sec><sec><title>Results</title><p><italic>MET</italic>ex14 was identified in 69 patients with lung cancer, including 53 adenocarcinoma (ADC) and 16 non-ADC patients. In comparison with patients without the <italic>MET</italic>ex14 mutation, lung cancer patients harboring the <italic>MET</italic>ex14 mutation were generally elderly individuals, never-smokers, and had poor performance scores. A higher frequency of <italic>MET</italic>ex14 mutations was detected in pulmonary sarcomatoid carcinoma (PSC) patients (24.3%, n = 9/37). However, stage IV PSC patients with or without the <italic>MET</italic>ex14 mutations showed similarly poor overall survival (OS) (<italic>p</italic> = 0.429). For all 36 <italic>MET</italic>ex14-positive lung ADCs, multivariate analysis showed several poor prognostic factors, including strong c-MET IHC staining (<italic>p</italic> = 0.006), initial brain metastasis (<italic>p</italic> = 0.005), and administration of only supportive care (<italic>p</italic> &lt; 0.001). After excluding seven patients who received only supportive care, we further analyzed 29 stage IV lung ADC patients with <italic>MET</italic>ex14 mutations who received anti-cancer treatment. Multivariate analysis showed that pemetrexed treatment (<italic>p</italic> = 0.003), lung radiotherapy (<italic>p</italic> = 0.020), initial brain metastasis (<italic>p</italic> = 0.005), and strong c-MET IHC staining (<italic>p</italic> = 0.012) were independent prognostic factors for OS in these patients.</p></sec><sec><title>Conclusions</title><p>A higher frequency of <italic>MET</italic>ex14 mutations was detected in PSC patients. Stage IV PSC patients with or without the <italic>METex14</italic> 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 <italic>MET</italic>ex14 mutation.</p></sec>