基于新型分子探针联合检测的肝细胞癌肿瘤免疫微环境综合分析方法研究

Currently, over half of all the cases of hepatocellular carcinoma (HCC) are from our country. The difficulty in the diagnosis and control of HCC is mainly due to its lengthy and unclear development. Great efforts have been devoted to understand this process and recently it has been discovered that during this process, a tumor-promoting microenvironment is formed to initiate and sustain the cancerogenesis of HCC. This microenvironment is characterized by the complicated interplay of the component cells, cytokines and the extracellular matrix. Although these interactions are more and more recognized as essential to improve our understanding of the pathology of HCC, the established methods are still focused on studying individual components of the microenvironment separately. Therefore in this project, it is planned to develop a multiplexed biosensing method using multiple low-molecular-weight probes, in order that multiple components of the microenvironment can be directly analyzed in the context of their interactions. By using this method, the interactions between various components of the microenvironment can be unraveled, and converging points in the signaling network of the microenvironment can be discovered to enable both more thorough investigation and more effective clinical control of HCC.

目前，一半以上的肝细胞癌病例来自我国。肝细胞癌一般源于长期、慢性肝部病变，该过程中会逐渐形成异常的免疫微环境，并通过微环境对肝细胞的异常免疫调控，造成受损肝细胞的过度修复、癌基因的积累并最终导致癌变。癌变之后，同样的微环境及失控的免疫调控机制赋予癌细胞免疫逃逸、免疫抑制等特性，并促进其侵袭、转移。因此微环境的免疫调控机制是阐明肝细胞癌病理、提高其诊疗水平的关键。微环境的免疫调控机制是由包含细胞、细胞因子与细胞外基质等多种因素构成的相互关联的复杂调控网络，然而目前相关研究中所采用的方法仍然侧重于将基本组成要素进行分割研究，缺乏针对微环境调控网络的整体研究手段。因此本项目拟利用多种低分子量分子探针的联合检测，对临床微环境样本中正在发生相互作用的各个要素进行综合分析，研究其相互作用，寻找微环境调控网络的关键节点，为肝细胞癌病理机制的阐明以及诊疗手段的升级提供关键技术支撑。

目前，一半以上的肝细胞癌病例来自我国。肝细胞癌一般源于长期、慢性肝部病变，该过程中会逐渐形成异常的免疫微环境，并通过微环境对肝细胞的异常免疫调控，造成受损肝细胞的过度修复、癌基因的积累并最终导致癌变。癌变之后，同样的微环境及失控的免疫调控机制赋予癌细胞免疫逃逸、免疫抑制等特性，并促进其侵袭、转移。因此微环境的免疫调控机制是阐明肝细胞癌病理、提高其诊疗水平的关键。微环境的免疫调控机制是由包含细胞、细胞因子与细胞外基质等多种因素构成的相互关联的复杂调控网络，然而目前相关研究中所采用的方法仍然侧重于将基本组成要素进行分割研究，缺乏针对微环境调控网络的整体研究手段。因此本项目拟利用多种低分子量分子探针的联合检测，对临床微环境样本中正在发生相互作用的各个要素进行综合分析，研究其相互作用，寻找微环境调控网络的关键节点，为肝细胞癌病理机制的阐明以及诊疗手段的升级提供关键技术支撑。