Prevalence of targeted therapy-related genetic variations in NSCLC and their relationship with clinicopathological characteristics

• Published in: PloS one Vol. 17; no. 1; p. e0262822
• Main Authors: Li, Fanghua, Ye, Peng, Cai, Peiling, Dong, Dandan, Zhang, Yihao, Yang, Yue, Sun, Xingwang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 21.01.2022; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - epidemiology; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - pathology; Adenocarcinoma of Lung - therapy; Aged; Alcohol; Analysis; Biology and Life Sciences; Biopsy; Bronchoscopy; Cancer therapies; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - therapy; Care and treatment; Chemotherapy; Crizotinib; Deletion; Diagnosis; Dosage and administration; Epidermal growth factor; Epidermal growth factor receptors; Female; Gender; Genetic diversity; Genetic variation; Glomerular filtration rate; Histology; Hospitals; Humans; Lung cancer; Lung cancer, Non-small cell; Lung diseases; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Male; Measurement; Medicine and Health Sciences; Metastasis; Middle Aged; Mortality; Mutation; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Non-small cell lung carcinoma; Pathology; Patients; Prevalence; Radiation therapy; Retrospective Studies; Risk factors; Sex Factors; Small cell lung carcinoma; Smoking; Squamous cell carcinoma; Standardization; Statistical analysis; Statistical methods; Subgroups; Tumors; China; United States > US
• DOI: 10.1371/journal.pone.0262822
• ISSN: 1932-6203

Non-small cell lung cancer (NSCLC) is the most common cancer type in China. Targeted therapies have been used to treat NSCLC for two decades, which is only suitable for a subgroup of patients with specific genetic variations. The aim of this study was to investigate the prevalence of genetic variations leading to sensitivity or resistance to targeted therapies in NSCLC, and their relationship with clinicopathological characteristics of the patients. Tumor samples were collected from 404 patients who were diagnosed to have NSCLC and underwent surgery, transthoracic biopsy, bronchoscopy biopsy, or pleural aspiration in Sichuan Provincial People's Hospital from January 2019 to March 2020. Commercial amplification-refractory mutation system kits were used to detect targeted therapy-related genetic variations in those tumor samples. The prevalence of genetic variations and their relationship with patient clinicopathological characteristics were analyzed using statistical software, followed by subgroup analysis. In all, 50.7% of the NSCLC patients had sensitive genetic variations to anti-EGFR therapies, and 4.9% of those patients had co-existing resistant genetic variations. Fusions in ALK, ROS1, or RET were found in 7.7% of the patients, including 2 patients with co-existing EGFR exon 19 deletion or L858R. EGFR exon 19 deletion and L858R were more common in female patients and adenocarcinoma. Further subgroup analysis confirmed the observation in female patients in adenocarcinoma subgroup, and in adenocarcinoma in male patients. In addition, smokers were more likely to have squamous cell carcinoma and KRAS mutation and less likely to have EGFR L858R, which were also confirmed after standardization of gender except KRAS mutations. Nearly half of the NSCLC patients were eligible for anti-EGFR treatments. In NSCLC, female gender and adenocarcinoma may indicate higher chance of EGFR exon 19 deletion or L858R, and smoking history may indicate squamous cell carcinoma and EGFR L858R.