血浆循环DNA外显子组突变影响肝癌转移复发机制研究

筛选能便捷应用于临床的肝癌转移复发标志物、寻找特异药物靶点、提供个体化防复发手段是进一步提高肝癌疗效的关键。本研究组前期研究发现，HTPAP基因tagSNP+357C/G GG+GC基因型可作为肝癌转移复发的临床预测指标，HTPAP启动子SNP对基因的转录活性也有显著影响，提示基因的遗传变异可影响基因的表达和功能。但我们同时发现，我们筛选出的SNP位点并不在基因的外显子功能区。基于我们前期已证实血浆循环DNA可以用来反映肿瘤组织的微卫星变异，我们拟采用全基因组外显子测序的方法分析血浆循环DNA外显子突变与肝癌转移复发的相关性，探索其相关机制并构建能预测肝癌转移复发的外周血"肇事突变组合"芯片和能指导靶向药物使用的个体化防复发策略。该研究不仅是前期工作基础上的进一步深入研究，而且还可能为肝癌的分子分型、肿瘤转移复发的分子预测、靶向药物的个体化应用提供新的方法，实现基础研究的临床转化。

Screening markers of clinical hepatocellular carcinoma metastasis and recurrence and determining specific drug targets are important in improving the treatments of hepatocellular carcinoma (HCC), even in providing individualized treatment to prevent its recurrence. Our Previous study showed that the HTPAP tagSNP+357C/G GG+GC genotypes can be used to predict tumor metastasis and prognosis in HCC patients. The SNPs of HTPAP promoter also have significant effects on the transcriptional activity of the gene. We also verified that the microsatellite alterations in the tumor tissue of HCC could be detected in the corresponding circulating plasma DNA. In the present study, the exome sequencing is going to be used in circulating plasma DNA to investigate the association of exome mutation with metastasis and recurrence of hepatocellular carcinoma. By constructing gene chips of the driver mutation pattern, a new strategy may be presented to study the molecular typing, prediction the metastasis and recurrence of HCC, and also guide individualized anti-relapse treatment of HCC patients for translational medicine research.