Liaoning Medical University, Jinzhou 121000, PR China.
Oncol Rep. 2012 Apr;27(4):979-86. doi: 10.3892/or.2011.1591. Epub 2011 Dec 13.
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.
我们研究了 BAG-1 表达与非小细胞肺癌（NSCLC）患者对铂类化疗药物敏感性的相关性。采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法分别检测 NSCLC 术后患者（I-IIIA 期）或健康受试者肺组织中 BAG-1 的 mRNA 和蛋白表达。Cox 回归分析用于量化 NSCLC 患者生存预后因素与生存的相关性。收集新诊断为晚期 NSCLC（IIIB-IV 期）患者化疗前的静脉血样，分析等位基因频率和基因多态性。与健康对照组（11.67%，14 例）相比，NSCLC 患者肺组织中 BAG-1 的 mRNA 和蛋白水平明显升高（61.67%，74 例）（χ²=5.601，P<0.05）。此外，BAG-1 表达被确定为 NSCLC 患者生存的独立预后因素。由于进展时间和生存率显著提高，阳性表达 BAG-1 的患者的生存期延长（TTP，49.3 个月；5 年生存率，16.21%），而无 BAG-1 表达的患者则无（χ²=7.243，P<0.05）。鉴定并证实了两种 BAG-1 消化模式（CC 和 CT）。患者（77.46%）在 BAG-1 密码子 324 处为 C/C 基因型，而 22.54%为 C/T 基因型。这些患者中不存在 T/T 基因型。携带 BAG-1 密码子 324 处 C/C 基因型的患者的进展风险是携带 C/T 基因型的患者的 1.87 倍（P<0.001）。随访检查显示，携带 C/C 基因型的患者的化疗敏感性是携带 C/T 基因型的患者的 2.852 倍（95%CI，1.133-7.182；P=0.026）。这两组患者的中位无进展生存期（PFS）和总生存期（OS）存在显著差异。与携带 BAG-1 的 C/T 基因型的患者相比，携带 BAG-1 密码子 324 处 C/C 基因型的患者对铂类化疗药物有更好的反应。因此，BAG-1 的表达与 NSCLC 患者对铂类化疗药物的敏感性密切相关。
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