肝细胞肝癌诊断标志物TAA的筛选、鉴定与临床验证研究

Primary hepatocellular carcinoma is one of the most common cancers in our country. Since signs and symptoms in early stage are not obvious,the majority of patients with HCC are usually found in the late course, for them the average time from the discovery to death is only 3-6 months,so early diagnosis and treatment is very important. In human blood, there are not only the tumor-associated antigens (TAAs), but also corresponding autoantibodies. in theory, all of them can be used as tumor markers,but in fact TAAs are not stable in circulation because they will soon be degraded after released from tumor cells or be cleared within a short time, while the corresponding autoantibodies occur in the early stage of tumor, and in serum of normal and non-cancer patients the titer of these autoantibodies is very low even is not in existence ,so autoantibodies can be used as serum markers for diagnosis of tumors. Although serum alpha fetoprotein (AFP) is widely used to detect HCC, the sensitivity is only 60%, and the specificity is also not optimal. Based on previous studies, Our group will use proteomics and a combined application of magnetic beads with MALDI-TOF MS technique to screen and identify hepatocellular carcinoma TAAs, analyze this antigens in the gene, protein and tissue level, and design a mini-array of multiple TAAs to detect corresbonding autoantibodies,then explore the possibility when it used as a method for early diagnosis of hepatocellular carcinoma, in order to lay theoretical and practical basis for the establishment of a new non-invasive liver cancer early immunodiagnosis technology.

原发性肝细胞肝癌（HCC）是常见的恶性肿瘤之一，早期症状体征不明显，又缺乏特异的早期诊断方法，大多数患者发现时病程已为晚期，生存期仅3-6个月。在人体外周血中，存在肿瘤相关抗原(TAA)，也有相应的自身抗体，理论上它们均可作为肿瘤标志物，实际上TAA被肿瘤细胞释放后很快被降解，或者进入血循环后很短时间内被机体清除，不能稳定存在；而相应的自身抗体出现在肿瘤发生早期，且在正常人和非肿瘤患者血清中不存在或者滴度很低，可作为血清标志物来诊断肿瘤。目前甲胎蛋白（AFP）诊断肝癌的灵敏度仅60%，特异性不高。本课题组在既往研究的基础上将运用蛋白质组学和磁珠结合质谱技术，筛选、鉴定HCC的TAA，并从基因、蛋白和组织水平进行分析，从而设计出一组针对HCC的特异性TAA组合，检测TAA组合抗体，评价其作为HCC早期免疫诊断标志的可行性，为建立一种新的HCC体外非侵入性免疫诊断技术奠定理论依据和实践基础。

原发性肝细胞肝癌（HCC）是常见的恶性肿瘤之一，早期症状体征不明显，又缺乏特异的早期诊断方法，大多数患者发现时病程已为晚期，生存期仅3-6个月。HCC的肿瘤相关抗原(TAA)及相应自身抗体可作为血清标志物来诊断肿瘤。本课题组在既往研究的基础上，运用LC-MS/MS和iTRAQ技术，筛选鉴定HCC的TAA及其抗体，并从基因、蛋白和组织水平进行分析，同时筛选鉴定HCC的差异表达蛋白。我们进一步评价了所筛分子作为HCC早期诊断、疾病监测和疗效评价生物标志物的可行性。这些结果为建立一种新的HCC体外非侵入性诊断、监测技术奠定理论依据和实践基础。