免疫相关蛋白CMTM6在肝细胞癌恶性进展中的作用及机制研究

肝癌是消化系统常见的恶性肿瘤，其高侵袭性、高转移复发及生存期短一直是困扰临床的难点和热点。前期实验发现，CMTM6在肝癌中表达下调可能与侵袭转移和预后密切相关；细胞功能学实验发现CMTM6表达变化与细胞增殖、侵袭和迁移能力等肿瘤生物学行为有关；全基因组芯片检测发现，CMTM6可能通过IL-17F等免疫信号通路促进肝癌侵袭转移，有望成为肿瘤诊治的潜在新靶标。本项目通过体内外实验探讨CMTM6表达变化对肝癌细胞生物学特性的影响；利用全基因组芯片筛选并验证CMTM6与相关信号通路、靶基因及免疫因子的关系，阐明CMTM6在肝癌恶性进展中的作用及调控机制；采用大规模肝癌样本的关联研究，建立包含分子事件和环境暴露的多因素肝癌发病风险评估模型，对肝癌手术存活患者进行前瞻性随访，验证CMTM6及免疫相关通路靶点在肝癌恶性进展中的作用及临床意义，为开发临床可用的诊断指标和治疗靶点提供原创性的理论和技术依据。

Hepatocellular carcinoma (HCC) is a common malignant tumor of digestive system. The high invasiveness, high metastasis, high recurrence, and poor survival of HCC has been the difficulty and hot spot in HCC clinical. Our previous experiments found that down-regulation of CMTM6 in HCC tissues was closely related to HCC invasion, metastasis and prognosis. Cell functional assays showed that deregulated expression of CMTM6 was related to tumor biological behaviors, such as cell proliferation, invasion and migration. Gene chip sequencing results indicated that CMTM6 might promote HCC metastasis through IL-17F signaling pathway. These previous results suggest that CMTM6 can become a novel biomarker in HCC occurrence and development. The purpose of this project is to explore the effect of cmtm6 expression changes on the biological characteristics of hepatocarcinoma cells in vitro and in vivo; to screen and verify the relationship between CMTM6 and related signal pathways, target genes and immune factors by using the whole genome microarray, to clarify the role and regulatory mechanism of CMTM6 in the progression of hepatocarcinoma malignancy, Using large-scale correlation study of HCC samples, a multi factor risk assessment model of HCC including molecular events and environmental exposure was established, The patients who survived the operation of HCC were followed up prospectively to verify the role and clinical significance of CMTM6 and immune related pathway targets in the progression of HCC, Our project will provide an original theoretical and technical basis for the development of clinically available diagnostic indicators and therapeutic targets.