Key Laboratory of Gene Engineering of the Ministry of Education, School of Life Sciences, Sun Yat-sen (Zhongshan) University, Xin Gang Xi Road 135#, Guangzhou 510275, Guangdong Province, China.
World J Gastroenterol. 2010 Dec 28;16(48):6104-10. doi: 10.3748/wjg.v16.i48.6104.
to investigate the effect of the G-1666A polymorphism in the multidrug resistance related protein-1 (MRP1) on outcome of hepatocellular carcinoma (HCC).
a cohort of 162 patients with surgically resected HCC who received no postsurgical treatment until relapse was studied. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. Electrophoretic mobility shift assay (EMSA) was used to evaluate the influence of the G-1666A polymorphism on the binding affinity of the MRP1 promoter with its putative transcription factors.
Kaplan-Meier analysis showed that patients with GG homologues had a reduced 4-year disease-free survival compared with those carrying at least one A allele (P = 0.011). Multivariate Cox regression analysis indicated that the -1666GG genotype represented an independent predictor of poorer disease-free survival [hazard ratio (HR) = 3.067, 95% confidence interval (CI): 1.587-5.952, P = 0.001], and this trend became worse in men (HR = 3.154, 95% CI: 1.604-6.201, P = 0.001). A similar association was also observed between 4-year overall survival and the polymorphism in men (HR = 3.342, 95% CI: 1.474-7.576, P = 0.004). Moreover, EMSA suggested that the G allele had a stronger binding affinity to nuclear proteins.
the MRP1 -1666GG genotype predicted a worse outcome and was an independent predictor of poor survival in patients with HCC from Southeast China.
探讨多药耐药相关蛋白 1（MRP1）中的 G-1666A 多态性对肝细胞癌（HCC）患者预后的影响。
研究了 162 例接受手术切除且术后未接受任何治疗直至复发的 HCC 患者。通过聚合酶链反应-限制性片段长度多态性分析进行基因分型。电泳迁移率变动分析（EMSA）用于评估 G-1666A 多态性对 MRP1 启动子与其假定转录因子结合亲和力的影响。
Kaplan-Meier 分析表明，与携带至少一个 A 等位基因的患者相比，GG 同型患者的 4 年无疾病生存率降低（P = 0.011）。多变量 Cox 回归分析表明，-1666GG 基因型是无疾病生存率较差的独立预测因子[风险比（HR）= 3.067，95%置信区间（CI）：1.587-5.952，P = 0.001]，这种趋势在男性中更为明显（HR = 3.154，95%CI：1.604-6.201，P = 0.001）。该多态性与男性患者的 4 年总生存率之间也存在类似的关联（HR = 3.342，95%CI：1.474-7.576，P = 0.004）。此外，EMSA 表明 G 等位基因与核蛋白具有更强的结合亲和力。
MRP1-1666GG 基因型预示着更差的结局，是中国东南部 HCC 患者生存不良的独立预测因子。
