Impact of glutathione S transferases P1 (Ile105Val) variants on the risk of GSTp, phosphorylated c-Jun kinase, and P53 phenotypic expression and their implications on overall survival outcomes in non-small cell lung cancer patients treated with chemotherapy

Abstract

AimThis study focused on GST-M1, T1 null, and P1 Ile105Val variant genotypes associated with the risk of altered expression of GSTp, pJNK, and P53 in NSCLC patients. These markers and overall survival (OS) were correlated with a key set of clinicopathological characteristics. MethodsGenotyping of GST- M1, T1 (+/−), and P1 (Ile105Val) was performed using PCR-RFLP.The expression of GSTp, pJNK, and P53 phenotypes was assessed by immunohistochemistry. The Spearman test was used to examine the correlation between GSTp, pJNK, and P53. Kaplan-Meier test was used for OS analysis. ResultsGSTP1 Val/Val and Ile/Val genotypes notably increased GSTp expression by 1.8 and 1.7 fold, respectively (p = 0.04,p = 0.06). GSTP1 Val/Val and Ile/Val genotypes considerably reduced P53 expression by 0.61 and 0.57 fold, respectively (p = 0.03& p = 0.05), respectively. GSTp, pJNK, and P53 were significantly co-expressed (p < 0.001). GSTp and pJNK expression showed a moderate negative correlation (ρ = −0.32, p = 0.046). In contrast, GSTp and P53 expression exhibited a strong negative correlation (ρ = −0.53, p < 0.0001). There was no correlation between P53 and pJNK expression(ρ = 0.07, p = 0.54). The patient’s median OS was 8.9 months, and it was significantly related to pack-years, stage, metastasis, and GSTM1(-/-) genotypes (p > 0.05). SQCLC showed poor OS than ADC (5.7 months vs.9.1 months, p = 0.2). Stage IV and metastasis significantly reduced the OS (p = 0.001). The tumour size and lymph nodes reflected poor OS (p = 0.07&p = 0.06). Gemcitabine+Cisplatin and Gefitinib showed a slightly higher rate of survival (9.3 months and 8.1 months) than Pemtrexe+Cisplatin treatment (7.0 months,p = 0.8). Multivariate analysis revealed that pack-years and GSTp were independent predictors for OS (p = 0.03). ConclusionGSTp, pJNK, and P53 showed interconnected cascading. Age, pack-year, stage, and GSTp were found to be significant predictive factors for OS.Pack-years, GSTp independent OS predictor.