Possible Associations between PD1/PDL1 Gene Variants, Gene Expression, and Protein Expression and Clinical Outcome of Non-Small-Cell Lung Cancer

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This study aimed to investigate the polymorphisms and protein expression of PD-1/PD-L1 molecules concerning non-small-cell lung cancer (NSCLC) susceptibility and their potential relationship with clinical parameters. PD-1 (rs2227981) and PD-L1 (rs2890658) gene variants were genotyped using PCR and RFLP in 80 NSCLC patients and 79 healthy controls. Serum soluble PD-1 levels were measured by ELISA, and PD-L1 protein expression was analyzed via Western blot. Clinical parameter differences between NSCLC cases and controls were evaluated. The PD-L1 A/C AA genotype frequency was significantly higher in patients than in controls (P = 0.043). In PD-1 C/T variants, the CC genotype was more prevalent in cases with lymphovascular invasion than those without (P = 0.028), while the CT genotype was more frequent in patients without lymphovascular invasion (P = 0.047). Additionally, the CC genotype was associated with perineural invasion (P = 0.026). Serum PD-1 levels were significantly elevated in patients with the CC genotype for PD-1 C/T compared with controls (P = 0.008). Combined genotype analysis revealed that the CTAC genotype was more common in the control group than in NSCLC patients (P = 0.016). Moreover, PD-L1 protein expression was significantly higher in tumor tissues than controls (P < 0.0001). These findings suggest that PD-1 and PD-L1 polymorphisms and their expression levels may play crucial roles in NSCLC susceptibility and progression. Understanding these molecular mechanisms could contribute to developing novel therapeutic strategies for NSCLC patients.