癌、炎外周血CD4T细胞免疫功能损伤特征及个体化癌、炎鉴别诊断标志识别

项目名称： 癌、炎外周血CD4T细胞免疫功能损伤特征及个体化癌、炎鉴别诊断标志识别

项目编号： No.81501829

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 洪贵妮

作者单位： 福建医科大学

项目金额： 18万元

中文摘要： 由于癌、炎患者的外周血中都存在髓系细胞增加淋巴系细胞减少的现象，它们相对正常对照的基因差异表达信号高度相似，都主要反映髓系和淋巴系细胞间的差异，难以应用于鉴别癌、炎两类疾病。在预实验中，通过分析多种癌、炎疾病的外周血CD4T细胞等淋巴细胞的基因表达谱，我们发现癌、炎外周血免疫细胞存在完全不同的基因异常表达模式与功能特征。在本课题中，我们拟揭示在正常外周血CD4T细胞中基因表达的相对大小秩序关系存在广泛的稳定性（反映正常细胞中基因表达的协调关系），据此设计算法识别基因表达协调关系显著异常的疾病相关通路，应用于分析癌、炎外周血CD4T细胞的功能损伤共性差异特征及是否存在癌、炎（如胃癌与胃炎）特异的特征；最后，发展基于个体化通路分析的识别癌、炎鉴别标志的方法，应用于识别胃癌与胃炎的个体化鉴别标志。本课题的研究内容对探究肿瘤外周血免疫细胞功能损伤特征及识别癌、炎鉴别的分子标志兼具理论与应用价值。

中文关键词： 癌症；炎症；外周血CD4T细胞；疾病标志；个体化诊断

英文摘要： As the proportions of myeloid and lymphoid cells increased and decreased respectively in peripheral whole blood of both cancer and inflammation, the differential mRNA signals observed in peripheral whole blood samples from cancer patients and from inflammatory patients compared to healthy controls were similar, all mainly reflecting the expression differences between myeloid cells and lymphoid cells. Therefore, it may be difficult for whole-blood gene expression signatures to distinguish cancer from inflammation. By analysing expression profiles of CD4 T cells for multiple cancer/inflammation, we found that the abnormal gene expression patterns and different dysfunctions exist in cancer and inflammation immune cells. Here, we will first show that the relative expression orderings of gene pairs are extensively stable in normal blood CD4 T cells, reflecting the coordinated gene expression in normal cells. Then, we will develop methods for identifying disease related pathways whose coordination of gene expression is significantly disturbed. We will apply the proposed methods to analyse the common difference of functional defect in cancer and information CD4 T cells and investigate whether there is a cancer specific signature that could discriminate cancer from inflammation (such as gastric cancer and gastritis). Finally, we will develop methods to identify discriminable biomarkers between cancer and inflammation based on personalized pathway analysis. Results of this research would have extensive theoretical and practical values for the investigation of functional defect characteristics in cancer immune peripheral blood cells and for the identification of biomarkers for diagnosis of cancer and inflammation.

英文关键词： cancer;inflammation;peripheral blood CD4 T cells;disease biomarker;personalized diagnosis