Influence of GSTP1 Polymorphism on the Clinical Outcomes of Patients With Advanced NSCLC Receiving First-Line Bevacizumab-Based Regimen: A Real-World Retrospective Study

Abstract

Background: This study was to investigate the influence of GSTP1 gene polymorphism on the clinical outcomes of patients with advanced non-small-cell lung cancer (NSCLC) receiving first-line bevacizumab plus chemotherapy regimen. Methods: A total of 128 patients with advanced NSCLC who were administered with bevacizumab-based first-line regimens were recruited in this study. Available blood specimen and peripheral blood mononuclear cells (PBMCs) of the patients were obtained for the analysis of polymorphism and GSTP1 gene mRNA expression, respectively. The association between genotype status and clinical outcomes and other variates was analyzed and presented. Results: The prevalence of rs1695 were in accordance with Hardy-Weinberg Equilibrium ( P = .978). Patients with GG and AG genotypes were merged in a pattern of dominant inheritance to seek for the potentially clinical significance. Analysis of efficacy exhibited that the objective response rate (ORR) of patients with AA genotype and AG/GG genotypes were 62.1% (54/87) and 51.2% (21/41) ( P = 0.245). Prognosis demonstrated that the median progression-free survival (PFS) of patients with AA genotype and AG/GG genotypes were 9.5 and 5.6 months, respectively ( P = .007). Furthermore, the median overall survival (OS) of the two genotypes were 22.0 and 16.6 months, respectively ( P = .003). In addition, adjusted in multivariate Cox analysis for OS, AG/GG genotype was an independent factor for OS. Interestingly, mRNA analysis suggested that the mRNA expression of GSTP1 in PBMC of the patients with AG/GG genotypes of rs1695 polymorphism was significantly higher than those of patients with AA genotype ( P < .001). Conclusion: GSTP1 polymorphism rs1695 could be used for the prognostic evaluation of patients with advanced NSCLC receiving bevacizumab combined chemotherapy regimen.