从免疫浸润角度分析肝癌患者性别和预后生存关系的差异

Analysis of the Relationship between Gender and Prognostic Survival in Patients with Hepatocellular Carcinoma from the Perspective of Immune Infiltration

基于生物信息学的手段从免疫浸润角度分析肝癌患者的性别和预后生存关系的差异.从TCGA数据库中的肝癌和正常组织的免疫浸润微阵列数据、TMB数据,使用CiberSort软件提取其中的免疫细胞基因信息,并进行肝癌患者性别和预后生存关系的差异分析.发现肝癌微环境中的免疫激活可能更多来自活化NKT细胞且与预后有关,并有显著的性别差异;同时微环境免疫抑制可能与肝癌组织中巨噬细胞M1被显著抑制有关.此外,本研究还发现男性肝癌患者中记忆B细胞、活化NK细胞、DC细胞均较女性少,提示男女肝癌发病以及预后差异的原因是性激素影响肝癌组织的特异性以及体液免疫细胞的差异性激活导致的.此外,研究了肝癌突变负荷(TMB)性别差异情况,分析结果显示TMB和男性生存预后明显相关,却和女性不相关.对男女性特有的15个下调和82个上调的差异基因进行DAVID富集分析,发现与男性生存明显相关的下调特异基因是DACH1,上调特异基因是VLDLR和SOX2,这些肿瘤差异基因可以和募集来的免疫细胞相互作用,从而改变肿瘤微环境,导致男女性的发病率和预后差异.

This study analyzed the differences between gender and prognostic survival relationship of liver cancer patients from the perspective of immune infiltration based on bioinformatics methods. Based on the immune infiltration microarray data and TMB data of liver cancer and normal tissues in the TCGA database, we used the software CiberSortto extract the immune cell gene information, and analyzed the difference between gender and prognostic survival of liver cancer patients. It was found that the immune activation in liver cancer microenvironment was more likely to come from activated NKT cells and related to prognosis, and there were significant gender differences. At the same time, microenvironmental immunosuppression might be related to the significant inhibition of macrophage M1 in liver cancer tissues. In addition, fewer memory B cells, activated NK cells, and DC cells were found in male liver cancer patients than female patients, which suggests that the reason for the difference in the incidence and prognosis of liver cancer in men and women is the specificity of sex hormones affecting liver cancer tissues and differential activation of humoral immune cells. Then, gender differences in liver cancer mutational load(TMB) were studied. The analysis results showed that TMB was significantly related to the survival prognosis of men, but not to women. By DAVID enrichment analysis of 15 down-regulated and 82 up-regulated differential genes specific to men and women,we found that the down-regulated specific genes that are significantly related to male survival are DACH1, and the up-regulated specific genes are VLDLR and SOX2. These tumor differential genes can interact with the recruited immune cells and alter the tumor microenvironment, which leads to differences in the incidence and prognosis of men and women.