CD147及其相关分子群遗传多态性与肝癌TACE联合利卡汀治疗预后的相关性及作用机制

The majority of hepatocellular carcinoma ( HCC ) are diagnosed at advanced stage and only small proportions of HCC patients are suitable candidates for surgery. Transcatheter arterial chemoembolization ( TACE ) combined with Licartin has been used as a palliative treatment for patients with unresectable HCC and showed good efficacy. However, therapeutic effects and prognostic factors for HCC patients treated with TACE combined Licartin have not been clarified presently. Our previous study showed that CD147 (target of Licartin) and its related pathway molecules were closely related with HCC development, invasion and metastasis, treatment response and prognosis. We hypothesize that single nucleotide polymorphisms ( SNP ) of CD147 related molecules may be used as surrogate biomarkers of the genetic background of HCC patients to predict the therapeutic response and prognosis. In this study, functional SNPs in CD147 related genes will be selected using a set of Web-based SNP selection tools, by which we can select SNPs based on linkage disequilibrium and predicted functional characteristics of both coding and noncoding SNPs. Genotyping for 1000 HCC patients will be performed using the iPLEX genotyping system. We will further evaluate the association between genetic variations in CD147 related genes and the overall survival and therapeutic effects of HCC patients, and then cell model and vivo analysis will be used to elucidate the molecular mechanisms. The results will help us to select unresectable HCC candidates to receive TACE combined Licartin to achieve the maximum therapeutic benefits.

大多数肝细胞癌（HCC）患者确诊时已属中晚期而丧失根治性手术治疗机会。经导管动脉化疗栓塞（TACE）联合放射免疫靶向治疗药物利卡汀已成为HCC非手术治疗的一种新方法，显示出良好疗效。然而，不同患者的疗效及预后存在较大的个体差异。如何有效预测预后并采取个体化治疗是提高HCC整体治疗效果的关键。本项目组前期研究工作证实：利卡汀的靶抗原CD147及其相关通路分子与HCC的发生发展、侵袭转移、治疗反应及预后密切相关，其遗传多态性（SNP）有可能作为潜在标志物用于疗效预测。本项目拟利用基因质谱技术平台高通量检测HCC患者CD147及其相关分子群的功能性SNP及标签SNP，并结合病人临床治疗情况及随访资料，分析其与TACE联合利卡汀治疗HCC的疗效及病人预后的相关性；再利用细胞及动物模型分析其特定遗传变异位点影响疗效及预后的分子机制，为真正实现该治疗方法在临床上应用的个体化提供实验依据。

147及其相关分子群的功能性及标签遗传多态性（SNP），结合病人临床及随访资料，分析其与TACE联合利卡汀治疗的疗效及预后的相关性，为个体化治疗提供实验依据。本次研究中主要完成了对1000例肝癌患者行TACE治疗的临床资料随访信息的整理及收集，并完成了关于CD147相关基因CD147（rs2229664、rrs8259、rs8637、rs28915400）、ASCT2（rs3826793、rs2070246）、MCT1（rs1049434、rs60844753）MCT2（rs1000708、rs3763980、rs7976956）、MCT4（rs9907757、rs116904469、rs11077983）等相关SNP位点的检测，并进行统计研究。并撰写相关论文8篇。其对于利卡汀患者预后有着重要的意义。