Expression and clinical significance of programmed cell death protein 1/programmed death-ligand 1 in non-small cell lung cancer patients with rare mutations of epidermal growth factor receptor gene: A retrospective cohort study.

Abstract

Objective: Lung cancer represents a major global health issue and serves as a leading cause of cancer-related deaths, with non-small cell lung cancer (NSCLC) accounting for a considerable proportion of these cases. This study aimed to investigate the expressions and clinical importance of programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) in patients with rare mutations of the epidermal growth factor receptor (EGFR) gene in NSCLC.

Material and methods: A retrospective analysis including 121 NSCLC patients with rare EGFR mutations was performed. Immunohistochemistry was conducted to assess PD-L1 expression, and patients were categorized into PD-L1-negative (PLN, n = 95) and PD-L1-positive (PLP, n = 26) groups. PD-1 expression was also evaluated, with patients divided into PD-1-negative (PN, n = 93) and PD-1-positive (PP, n = 25) groups. The associations among PD-L1/PD-1 expression and demographic characteristics, progression-free survival (PFS), overall survival (OS), and a 5-year survival period were analyzed.

Results: Significant negative correlations were observed between PD-L1 expression and PFS (r = -0.202, R² = 0.041, P = 0.026) and OS (r = -0.204, R² = 0.042, P = 0.024). The PLN group exhibited a significantly longer PFS (13.47 ± 3.58 months) than the PLP group (11.67 ± 3.67 months; t = 2.222, P = 0.032) and longer OS (21.39 ± 5.69 months) compared with the PLP group (18.65 ± 4.32 months; t = 2.664, P = 0.010). For PD-1 expression, a negative correlation with PFS was noted (r = -0.325, R² = 0.106, P < 0.001). The PN group displayed longer PFS (14.36 ± 3.18 months) and OS (21.71 ± 5.82 months) compared with the PP group (PFS: 11.98 ± 3.72 months, OS: 20.01 ± 5.18 months).

Conclusion: This study underscored the importance of PD-1 and PD-L1 expression as prognostic and predictive markers in NSCLC patients with uncommon EGFR mutations. These biomarkers are crucial for achieving informed treatment choices and enhancement of prognostic evaluations in this specific group.