Association Between Smoking Status and PD-L1 Expression in Metastatic Driver Mutation Negative Non-Small Cell Lung Cancer: A Real-World Cohort Study
Selahattin Çelik11Department of Medical Oncology, Ankara Etlik City Hospital, Ankara, Türkiye
Objectives: Programmed cell death-1 (PD-L1) expression has become a key predictive biomarker for immunotherapy; however, the clinical and biological factors influencing its expression remain incompletely understood. Tobacco smoking is associated with extensive genomic alterations and increased tumor mutational burden (TMB), which may influence immune checkpoint signaling and tumor immunogenicity. Methods: In this retrospective observational study, patients with stage IV driver-mutation-negative NSCLC treated at a tertiary oncology center were included. Clinical and pathological variables including age, sex, smoking status, histological subtype, Eastern Cooperative Oncology Group performance status, and PD-L1 expression were collected from institutional medical records. PD-L1 expression was evaluated using immunohistochemistry and reported as tumor proportion score (TPS), categorized as <1%, 1–49%, and ?50%. Associations between smoking status and PD-L1 expression were analyzed using the chi-square test, and multivariable ordinal logistic regression was performed to identify independent predictors of PD-L1 expression. Results: A total of 333 patients with stage IV driver-mutation-negative NSCLC were included in the analysis. High PDL1 expression (TPS ?50%) was observed in 32 (43.2%) current smokers, compared with 18 (10.8%) former smokers and 4 (4.3%) never smokers, with a significant association between smoking status and PD-L1 expression categories (p<0.001). In multivariable ordinal logistic regression analysis adjusted for age, sex, and histological subtype, smoking status remained independently associated with higher PD-L1 expression (OR: 3.53, 95% CI: 2.44–5.11, p<0.001). Conclusion: Smoking status was independently associated with PD-L1 expression in patients with stage IV driver-mutation- negative NSCLC. Keywords: Biomarkers, immune checkpoint inhibitors, non-small cell lung cancer, PD-L1, smoking, tumor mutational burden
Cite This Article
Çelik S. Association Between Smoking Status and PD-L1 Expression in Metastatic Driver Mutation Negative Non-Small Cell Lung Cancer: A Real-World Cohort Study. EJMI. 2026; 10(4): 473-479
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