HLA-II类基因调控巨噬细胞在新疆哈族食管鳞癌浸润转移中的作用机制研究

The mortality of Kazakh esophageal carcinoma in Xinjiang was significantly higher than that of national average, and it has more inflammatory cell infiltrate, especially macrophages, which maybe related with Kazakh unique living environment and diet. Studies have shown that M2 macrophages with lower expression of HLA - class II genes in inflammatory microenvironment could promote the tumor invasion and metastasis, and its mechanism is still not fully proved. So this project to adopt macrophages and esophageal squamous cancer(ESCC) cells co-culture, observe the change of tumor cell morphology and invasiveness, then explore the effect of HLA-class II and CIITA methylation on macrophage differentiation regulation by using RNA interference, methyltransferase inhibitor and cell functional experiment, test the differential expression of invasion and metastasis related gene in JAK - STAT and NF-κB signaling pathway by using gene chip. At the same time, verify it in Kazakh ESCC tissues level. Eventually comprehensive evaluation the mechanism of HLA-II and CIITA methylation on macrophage regulation, infiltrate invasion and metastasis of Kazakh ESCC, Providing new ideas for prognosis estimation and immunogene therapy in Xinjiang Kazak esophageal carcinoma.

新疆哈族食管癌死亡率明显高于全国的平均水平，其食管癌及癌前病变炎症背景较重，间质巨噬细胞浸润明显，可能与哈族独特的居住环境和饮食习惯相关。研究显示炎性微环境中低表达HLA-II类基因的M2型巨噬细胞具有促进肿瘤浸润和转移的作用，其具体机制尚未完全探明。故本项目拟采用巨噬细胞和食管鳞癌细胞共培养，观察癌细胞形态、侵袭能力改变的基础上，利用RNA干扰、甲基化酶抑制途径和细胞功能实验观察HLA-II和CIITA甲基化对巨噬细胞分化调节作用；通过信号通路芯片检测干扰前后巨噬细胞JAK-STAT和NF-κB通路传导侵袭转移相关基因的差异性表达；同时在体内哈族食管鳞癌组织水平进行验证；探讨HLA-II类基因和CIITA甲基化介导巨噬细胞分化在食管鳞癌侵袭转移中的作用机制，为新疆哈族食管鳞癌预后判断和免疫基因治疗提供新的思路。