title: The role of expression and polymorphism of the BAG-1 gene in response             to platinum-based chemotherapeutics in NSCLC.
abstract: We investigated the correlation between BAG-1 expression and sensitivity to platinum-based chemotherapeutics in patients with non-small cell lung cancer (NSCLC). mRNA and protein expression of BAG-1 in lung tissue of NSCLC postoperative patients (I-IIIA stage) or healthy subjects were detected using reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. Cox regression analysis was used to quantify the association of prognostic factors with survival in NSCLC patients. Venous blood samples from patients newly diagnosed with advanced NSCLC (IIIB-IV stage) were collected before chemotherapy to analyze allelic frequency and gene polymorphisms. Compared to healthy controls (11.67%, 14 cases), levels of mRNA and protein of BAG-1 in lung tissues was significantly higher in NSCLC patients (61.67%, 74 cases) (χ²=5.601, P<0.05). Moreover, BAG-1 expression was identified as an independent prognostic factor for survival in NSCLC patients. As time to progression and survival rate was dramatically increased, patients with a positive expression of BAG-1 exhibited a prolonged survival period (TTP, 49.3 months; 5-year survival rat, 16.21%) compared with those without BAG-1 expression (χ²=7.243, P<0.05). Two BAG-1 digestion patterns (CC and CT) were identified and confirmed. patients (77.46%) had a C/C genotype at BAG-1 codon 324, while 22.54% had the C/T genotype. The T/T genotype was not present in these patients. The progression risk of patients carrying the C/C genotype at Bag-1 codon 324 was 1.87 times higher than that of patients carrying the C/T genotype (P<0.001). Follow-up examination showed that the chemotherapeutic sensitivity of patients carrying the C/C genotype was 2.852 times higher than that of patients carrying the C/T genotype (95% CI, 1.133-7.182; P=0.026). Significant differences were found in the median progression-free survival (PFS) and overall survival (OS) of these two cohorts of patients. Compared to patients carrying the C/T genotype of BAG-1, patients carrying the C/C genotype at Bag-1 codon 324 exhibited better responses to platinum-based chemotherapy. Hence, the expression of BAG-1 was closely associated with the sensitivity to platinum-based chemotherapeutics in NSCLC patients.
authors.affiliation: Liaoning Medical University, Jinzhou 121000, PR China.
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.forename: Min-Wen
authors.initials: MW
authors.lastname: Ha
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.forename: Wen-Lu
authors.initials: WL
authors.lastname: Zhang
authors.forename: Xue
authors.initials: X
authors.lastname: Cong
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Tong
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D017239:Paclitaxel / Q000008:administration & dosage; D010641:Phenotype; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics*; D016896:Treatment Outcome; D015854:Up-Regulation; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine
chemical_list: C091732:BCL2-associated athanogene 1 protein; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D014157:Transcription Factors; D014747:Vinblastine; D017239:Paclitaxel; D002945:Cisplatin; D000077235:Vinorelbine