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Implication of PD‑L1 polymorphisms rs2297136 on clinical outcomes of patients with advanced NSCLC who received PD‑1
Qiang Gong1, Hai-Ling Qie1, Shao-Yong Dong1
1Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China.
Abstract:
Clinically, programmed death-1 (PD-1) blockades have demonstrated promising therapeutic outcomes for patients with advanced non-small cell lung cancer (NSCLC). The present study aimed to examine the impact of programmed death-ligand 1 (PD-L1) polymorphism on clinical outcomes of patients with advanced NSCLC who were treated with PD-1 blockades therapy. The present study was designed as a retrospective analysis, where a consecutive screening of 89 patients with advanced NSCLC who received PD-1 blockades monotherapy were screened. Biological specimens were collected to determine the presence of polymorphism and PD-L1 mRNA expression through genotyping. The analysis focused on examining the relationship between the genotype status of PD-L1 polymorphism and clinical outcomes. Among the 89 patients with advanced NSCLC, the use of PD-1 blockades monotherapy resulted in objective response rate (ORR) of 22.5%, a median progression-free survival (PFS) of 3.4 months [95% Confidence Interval (CI): 1.80-5.00) and a median overall survival (OS) of 11.3 months (95% CI: 7.93-14.67). The analysis of polymorphism indicated that only rs2297136 had clinical significance. Among the 89 patients with NSCLC, the prevalence of rs2297136 was as follows: A total of 58 cases (65.2%) had the AA genotype, 28 cases (31.5%) had the AG genotype and 3 cases (3.4%) had the GG genotype. This resulted in a minor allele frequency of 0.19, which was in consistent with Hardy-Weinberg Equilibrium (P=0.865). The correlation analysis between genotype status of rs2297136 and clinical outcomes indicated that patients with the AA genotype had an ORR of 19.0%, while those with the AG/GG genotype had an ORR of 29.0% (P=0.278). Additionally, the median PFS for the AA genotype was 2.95 months, compared with 5.30 months for the AG/GG genotype (P=0.038). Accordingly, median OS of the AA and AG/GG genotypes was 8.8 and 18.4 months, respectively (P=0.011). The mRNA expression of PD-L1 was significantly higher in patients with AG/GG genotype compared with those with AA genotype (P<0.001). In clinical practice, PD-1 blockades demonstrated promising effectiveness in treating patients with advanced NSCLC. The presence of the rs2297136 variant in PD-L1 gene could potentially be used as a biomarker to predict the clinical outcomes of PD-1 blockades.
Insights
Programmed death-1 (PD-1) blockade therapy shows promise for advanced non-small cell lung cancer (NSCLC). PD-L1 rs2297136 polymorphism may predict treatment outcomes, with AG/GG genotypes showing improved progression-free and overall survival.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Programmed death-1 (PD-1) blockade therapy offers therapeutic benefits for advanced non-small cell lung cancer (NSCLC).
- The role of programmed death-ligand 1 (PD-L1) genetic variations in predicting treatment response remains an area of active investigation.
Purpose of the Study:
- To investigate the association between PD-L1 gene polymorphism, specifically rs2297136, and clinical outcomes in advanced NSCLC patients treated with PD-1 blockade monotherapy.
- To explore the correlation between PD-L1 rs2297136 genotypes and PD-L1 mRNA expression levels.
Main Methods:
- Retrospective analysis of 89 advanced NSCLC patients receiving PD-1 blockade monotherapy.
- Genotyping to determine PD-L1 rs2297136 genotype status and PD-L1 mRNA expression analysis.
- Statistical correlation analysis between genotype, PD-L1 expression, and clinical outcomes (objective response rate, progression-free survival, overall survival).
Main Results:
- Patients with AG/GG genotypes of rs2297136 exhibited significantly longer median progression-free survival (5.30 months vs. 2.95 months) and overall survival (18.4 months vs. 8.8 months) compared to AA genotype patients (P=0.038 and P=0.011, respectively).
- PD-L1 mRNA expression was significantly higher in patients with AG/GG genotypes (P<0.001).
- While objective response rates showed a trend favoring AG/GG genotypes (29.0% vs. 19.0%), this difference was not statistically significant (P=0.278).
Conclusions:
- The PD-L1 rs2297136 polymorphism is a potential predictive biomarker for clinical outcomes in advanced NSCLC patients treated with PD-1 blockade therapy.
- The AG/GG genotype of rs2297136 is associated with improved survival and higher PD-L1 mRNA expression, suggesting a role in treatment response.
- Further prospective studies are warranted to validate rs2297136 as a predictive biomarker in NSCLC immunotherapy.
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