Common driver mutations and programmed death-ligand 1 expression in advanced non-small cell lung cancer in smokers and never smokers

• Published in: BMC cancer Vol. 23; no. 1; p. 659
• Main Authors: Liam, Chong Kin, Yew, Chian Yih, Pang, Yong Kek, Wong, Chee Kuan, Poh, Mau Ern, Tan, Jiunn Liang, Soo, Chun Ian, Loh, Thian Chee, Chin, Ka Kiat, Munusamy, Vijayan, Liam, Yong Sheng, Ibrahim, Nur Husna
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 14.07.2023; BioMed Central; BMC
• Subjects: Adenocarcinoma; Anaplastic Lymphoma Kinase - genetics; Antibodies; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers; Biopsy; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Cigarette smoking; Cigarettes; Diagnosis; Dosage and administration; EGFR mutations; Epidermal growth factor receptors; ErbB Receptors - genetics; Female; Gene mutations; Genetic aspects; Health aspects; Histopathology; Humans; Kinases; Ligands; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - pathology; Male; Medical imaging; Metastasis; Monoclonal antibodies; Multivariate analysis; Mutants; Mutation; Non-small cell lung carcinoma; NSCLC; Patients; PD-L1; PD-L1 protein; Proteins; Retrospective Studies; Small cell lung carcinoma; Smokers; Smoking; Smoking status; Tomography; Tumors; Malaysia; Kuala Lumpur Malaysia; United States > US; Arizona; PD-L1; EGFR mutations; Smoking status; NSCLC
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-023-11156-y

In non-small cell lung cancer (NSCLC), there may be a relationship between programmed death-ligand 1 (PD-L1) expression, driver mutations and cigarette smoking. In this single-center retrospective study, the relationship between common driver mutations (EGFR mutation and ALK rearrangement) and PD-L1 expression in advanced NSCLC according to the patients' smoking history was examined. Light, moderate and heavy smokers had smoked < 20, 20-39, and ≥ 40 pack-years, respectively. The level of PD-L1 expression, assessed using Ventana SP263 monoclonal antibody assay, was defined by the tumor proportion score (TPS) as high expression (TPS ≥ 50%), low expression (TPS 1%-49%) and no expression (TPS < 1%). 101 (52.9%) of 191 advanced NSCLC patients were never smokers. EGFR mutations were more common in never smokers (64.4%) than in smokers (17.8%) with advanced NSCLC (P < 0.0001). A higher proportion of smokers (26.7%) had high PD-L1 expression compared to never smokers (13.9%) (P = 0.042). There was a trend for a higher proportion of male NSCLC patients [28 of 115 (24.3%)] than female patients [10 of 76 (13.2%)] to have high PD-L1 expression (P = 0.087]. High PD-L1 expression was seen in 32 of 110 (29.1%) patients with EGFR wild-type NSCLC but only in 6 of 81 (7.4%) patients with EGFR-mutant tumors (P < 0.0001). Among the 90 smokers with NSCLC, a higher proportion of heavy smokers (35.8%) than non-heavy smokers (13.5%) had high PD-L1 expression (P = 0.034). In patients with adenocarcinoma, high PD-L1 expression was seen in 25 of 77 (32.5%) patients with EGFR wild-type tumors but only in 4 of 70 (5.7%) patients with EGFR-mutant tumors (P < 0.0001). Among patients with adenocarcinoma, a significantly higher proportion of ever smokers (29.3%) than never smokers (13.5%) had high PD-L1 expression (P = 0.032). Among smokers with adenocarcinoma, a significantly higher proportion of heavy smokers (44.1%) than non-heavy smokers (8.3%) had high PD-L1 expression (P = 0.004). On multivariate analysis, after adjusting for gender and smoking status, heavy smoking and EGFR wild-type tumors remained significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma. Heavy smoking and EGFR wild-type tumors were significantly associated with high PD-L1 expression in NSCLCs and also in adenocarcinoma.