BCL-2 Associated athanogene 1 (BAG-1) and Xeroderma pigmentosum group D (XPD) are involved in the nucleotide excision repair pathway and DNA repair. We aimed to investigate whether polymorphisms in BAG-1 and XPD have effects on chemotherapy sensitivity and survival in patients with advanced non-small-cell lung cancer (NSCLC) treated with vinorelbine combined cisplatin (NP) regimen. A total of 142 patients with diagnosed advanced NSCLC were recruited in the current study. NP regimen was applied for all eligible patients. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for BAG-1 (codon 324) and XPD (codons 312 and 751) genotyping. The treatment response was evaluated according to the RECIST guidelines. Progression-free survival (PFS) and overall survival (OS) were record as median and end point, respectively. As for BAG-1 codon 324, the chemotherapy sensitivity in NSCLC patients with CT genotype was 0.383 times of those with CC genotype (P < 0.05). With respect to XPD codon 751, the chemotherapy sensitivity in NSCLC patients with Lys/Gln genotype was 0.400 times of those with Lys/Lys genotype (P < 0.05). In addition, NSCLC patients carrying combined C/C genotype at codon 324 in BAG-1, Asp/Asp of XPD codon 312, and Lys/Lys of XPD codon 751 produced a higher efficacy of NP chemotherapy compared to those carrying mutation genotypes (all P < 0.05). Further, there were significant differences in PFS between patients with combined C/C genotype of BAG-1 codon 324, Lys/Lys genotype of XPD codon 751, and Asp/Asp genotype of XPD codon 312 and patients carrying BAG-1 codon 324 C/T genotype, XPD codon751 Lys/Gln genotype, and XPD codon312 Asp/Asn genotype (P < 0.05). Multivariate Cox regression analysis indicated that the combined wild-type of codon 324 XPD, codon 751 XPD, and codon 312 BAG-1 is the protective factor for OS and PFS, and clinical stages is the risk factor for OS and PFS. In conclusion, our research demonstrated the combined effects of BAG-1 and XPD polymorphisms on chemotherapy sensitivity and survival in patients with advanced NSCLC, which might be the important predictive markers for platinum-based chemotherapy efficacy.
Keywords: Advanced non-small-cell lung cancer; BAG-1; Chemotherapy sensitivity; XPD.