title: Association between polymorphisms of BAG-1 and XPD and chemotherapy sensitivity in advanced non-small-cell lung cancer patients treated with vinorelbine combined cisplatin regimen.
abstract: 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.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Five Section of Renmin Street No. 2, Guta District, Jinzhou, 121000, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Oncology, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou, 121000, People's Republic of China.
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.affiliation: Department of Oncology, Binzhou Medical University Hospital, Binzhou, 256603, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Thoracic Surgery, Hubei Rongjun Hospital, Wuhan, 430079, People's Republic of China.
authors.forename: Jun-Chen
authors.initials: JC
authors.lastname: Chen
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Five Section of Renmin Street No. 2, Guta District, Jinzhou, 121000, People's Republic of China. haminwen_hmw@163.com.
authors.forename: Min-Wen
authors.initials: MW
authors.lastname: Ha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D014747:Vinblastine; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D002945:Cisplatin; D000077235:Vinorelbine
keywords: Advanced non-small-cell lung cancer; BAG-1; Chemotherapy sensitivity; XPD