| 王自义 汪鑫 刘晓南 何显力 瞿发林.单羧酸转运蛋白基因SNP 与肝细胞肝癌预后的关联研究[J].,2016,16(25):4840-4846 |
| 单羧酸转运蛋白基因SNP 与肝细胞肝癌预后的关联研究 |
| Correlation between Polymorphisms of Monocarboxylate Transporter Genesand Prognosis in Hepatocellular Carcinoma |
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| DOI： |
| 中文关键词: 单羧酸转运蛋白 单核苷酸多态性 肝细胞肝癌 预后 |
| 英文关键词: MCTs SNPs Hepatocellular carcinoma Prognosis |
| 基金项目:科技部国际科技合作项目（2013DFA32110） |
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| 中文摘要: |
| 目的：探讨单羧酸转运蛋白基因（monocarboxylate transporter, MCT）单核苷酸多态性（single nucleotide polymorphism, SNPs）
与肝细胞肝癌（hepatocellular carcinoma, HCC）根治术患者预后的关系。方法：运用Sequenom iPLEX 分型技术对830 例原发性
HCC患者MCT 家族（MCT1、MCT2 和MCT4）基因上的8 个功能性SNP 位点进行基因分型，并分析这些SNP 与HCC患者预后
的相关性。结果：MCT1 基因rs1049434 位点和MCT2 基因rs995343 位点基因型与HCC患者总体生存期及无复发生存期均显著
相关（P<0.05）。携带MCT1 AT 基因型或TT 基因型的患者死亡及复发风险均显著低于携带AA 基因型的患者（HR=0.72;
P=0.042 或HR=0.64; P=0.002）；携带MCT2 CT 基因型或TT 基因型的患者死亡及复发风险均显著高于携带CC 基因型的患者
（HR=1.64; P=0.018 或HR=1.52; P=0.026）。而且，MCT1 基因rs1049434 位点和MCT2 基因rs995343 位点对HCC预后存在显著
的累积效应，携带2 个危险基因型的患者死亡及复发风险分别是没有危险基因型患者的2.16 倍和2.54 倍。此外，携带2 个危险
基因型的HCC 患者在术后行TACE辅助治疗后死亡及复发风险均显著降低（P<0.05）。结论：MCT1 和MCT2 基因上的功能性
SNP位点有可能作为HCC 根治术后预后评估和TACE 辅助治疗反应预测的独立标志物。 |
| 英文摘要: |
| Objective:To explore the correlation between single nucleotide polymorphisms (SNPs) in monocarboxylate transporter
(MCT) genes and prognosis in hepatocellular carcinoma (HCC) after radical resection.Methods:Eight functional SNPs in 3 genes
(MCT1, MCT2 and MCT4) were selected and genotyped using the SequenomiPLEX genotyping systemin a cohort of 830 radical resected
HCC patients. Multivariate Cox proportional hazards model and Kaplan-Meier curve were used for the prognosis analysis. Cumulative
effect analysis was used for the multiple SNPs analysis.Results:Two individual SNPs, including rs1049434 in MCT1 and rs995343 in
MCT2, were significantly associated with overall survival (OS) and relapse-free survival (RFS) of HCC patients (all P < 0.05). Patients
carrying rs1049434 AT genotype or TT genotype had a significant decreased risk of death and relapse compared with those carrying the
AA genotype (HR = 0.72; P = 0.042 or HR = 0.64; P = 0.002, respectively); patients with rs995343 CT genotype or TT genotype showed
significantly worse OS and RFS than did those carrying CC genotype (HR=1.64; P = 0.018 or HR=1.52; P=0.026, respectively). MCT1
rs1049434 and MCT2 rs995343 SNPs had a cumulative effect of on HCC OS and RFS (P for trend < 0.001 for both). Those who carrying
two unfavorable genotypes (AT+TT for MCT1 and CC for MCT2) had 2.16-fold increased risk of death or 2.54-fold increased risk of relapse
compared with patients carrying no unfavorable genotypes (P=0.012 or P=0.001). Moreover, patients carrying 2 unfavorable genotypes
showed significant OS and RFS benefits from TACE therapy (all P<0.05).Conclusion:Our data suggest that functional SNPs in
MCT1 and MCT2 genes may serve as independent prognostic biomarkers in predicting clinical outcomes and the response to TACE therapy
for HCC patients who received radical resection. |
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