BAG-1基因多态性与晚期非小细胞肺癌患者铂类药物敏感性的关系

BAG-1 Genetic Polymorphisms Predict Clinical Responses to Platinum-Based Chemotherapy in Advanced Non-Small Cell Lung Cancer

目的:研究抗凋亡基因BAC-1324位点(C-T,rs11551682)基因多态性与晚期非小细胞肺癌(NSCLC)患者对含铂类化疗方案敏感性的关系,探讨其在晚期非小细胞肺癌化疗方案选择及预后中的意义。方法:以聚合酶链反应结合限制性片段长度多态性(PCR-RFLP)方法对142例经病理学确诊的晚期非小细胞肺癌患者BAG-1324位点基因多态性进行分析,采用紫杉醇/顺铂(TP)或长春瑞滨/顺铂(NP)的方案化疗,3个周期后进行临床疗效评价。用卡方检验等方法分析比较不同基因型与含铂化疗方案敏感性的关系。结果:142例晚期非小细胞肺癌患者中,BAG-1 codon324存在3种等位基因型,基因型频率分别为C/C77.46%(110/142)、C/T 22.54%(32/142)和T/T 0例;含铂化疗方案总有效率(CR+PR)为32.39%,其中CR 4例,PR 42例,SD 55例,PD4l例。携带BAC-1 codon 324 C/C基因型的个体对含铂化疗方案的化疗敏感性是BAG-1 codon324 C/T基因型携带者的2.852倍(95%CI1.133～7.182,P=0.026);携带BAG-l codon324 C/C基因型患者与C/T基因型患者PFS、OS差异有显著性统计学意义(5.7个月vs 5.3个月,P=0.002;8.1个月vs 7.7个月,P=0.013)。采用Cox回归模型进行多因素分析提示:BAG-1 Codon324位点基因型为C/T的患者疾病进展风险是C/C基因型患者的1.870倍(P=0.002)。结论:BAG-1 codon324基因多态性可能与晚期非小细胞肺癌患者对含铂化疗方案的化疗敏感性相关,携带C/T基因型患者可能预后不良。

Objective： To examine the association between genetic polymorphisms of BAG-1 and the clinical response to platinum-based chemotherapy for advanced non-small cell lung cancer （ NSCLC ）. Methods： In total, 142 patients with advanced NSCLC were routinely treated with paclitaxel/cisplatin or vinorelbine/cisplatin chemotherapy, and their clinical response was evaluated after 3 cycles. The codon 324 of BAG-Ⅰ was genotyped by polymerase chain reaction-restrictive fragment length polymorphism using DNA samples isolated from peripheral blood collected before treatment in 142 patients with advanced NSCLC. An unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical response. Results： Of the 142 patients, the frequencies of BAG-1 codon324 C/C, C/T, and T/T genotypes were 77.46% （ 110/142 ）, 22.54% （ 32/142 ）, and 0, respectively. The overall chemotherapeutic response rate （ CR ＋ PR ） among the patients was 32.39%, including 4 CR, 42 PR, 55 SD, and 41 PD. The response rate to chemotherapy was significantly higher in patients with the C/C genotype of the BAG-I codon 324 allele than in patients with the C/T genotype （ adjusted OR = 2.852; 95% CI： 1.133-7.182, P = 0.026 ）. There was a significant difference in the progression-free survival between patients with the C/C and C/T genotypes in BAG-1 codon324 （ 5.7 months vs. 5.3 months, P= 0.002 ）. Similarly, overall survival was better among patients with the C/C genotype than those with the C/T genotype （ 8.1 months vs. 7.7 months, P = 0.013 ）. Cox multivariate analysis showed that codon 324 of BAG-1 with the C/T genotype is associated with a higher risk of progression in NSCLC patients compared with the C/C genotype （ P= 0. 002 ）. Conclusion： Genetic polymorphisms in the codon 324 of BAG-1 may have significant effects on the clinical response of NSCLC patients receiving platinum-based chemotherapy and those with the C/T genotype may have poor prognosis.