基于TCGA数据库分析UHRF1基因在恶性胸膜间皮瘤中的表达及预后意义

利用生物信息学数据库分析泛素样含PHD和环指结构域蛋白1（UHRF1）在恶性胸膜间皮瘤（MPM）中的表达水平及临床意义。基于TCGA数据库和GTEx数据库差异表达分析UHRF1 mRNA在MPM组织和正常肺组织中的表达水平；使用R软件分析UHRF1 mRNA表达量与临床病理参数的相关性；构建Kaplan-Meier模型和单因素多因素COX回归模型分析UHRF1基因在MPM中的预后；利用TIMER2.0数据库分析UHRF1基因与免疫细胞浸润的关系； GSEA分析UHRF1基因发挥功能的主要富集通路。选取8例MPM组织及4例非MPM胸膜组织，通过RT-qPCR的方法验证UHRF1在MPM与非MPM胸膜组织的表达情况。数据库分析结果表明，与正常肺组织相比，UHRF1 mRNA在MPM组织中高表达； UHRF1高表达患者提示MPM患者预后不良；UHRF1基因表达量与CD4⁺辅助型T细胞2、CD4⁺效应记忆性T细胞、巨噬细胞等多种免疫细胞浸润水平具有显著的相关性（P ＜ 0.01），且显著影响MPM患者的预后。功能富集分析显示，UHRF1主要在DNA复制、蛋白酶体、同源重组等通路中起作用。在收集到的病例样本中，与非MPM胸膜组织相比，UHRF1 mRNA在MPM组织中的表达显著增高（P ＜ 0.001）。UHRF1在MPM组织中高表达，可能通过调节DNA甲基化和免疫细胞浸润来影响MPM患者预后，有望成为MPM治疗和预后评估的潜在靶点。

THE EXPRESSION AND PROGNOSTIC SIGNIFICANCE OF GENE UHRF1 IN MALIGNANT PLEURAL MESOTHELIOMA BASED ON TCGA DATABASE

To analyze the expression level and clinical significance of ubiquitin-like containing PHD and ring finger domain protein 1 (UHRF1) in malignant pleural mesothelioma (MPM) based on the bioinformatics database. The expression levels of UHRF1 mRNA in MPM tissues and normal lung tissues were analyzed based on the differential expression of TCGA database and GTEx database. R software was used to analyze the correlation between UHRF1 mRNA expression and clinicopathological parameters. Kaplan-Meier model and univariate multivariate COX regression model were used to analyze the correlation between UHRF1 and the prognosis of MPM. The relationship between gene UHRF1 and immune cell infiltration was analyzed by TIMER2.0 database. GSEA analyzed the main enrichment pathways of UHRF1 gene function. Eight cases of MPM tissues and four cases of non-cancerous pleural tissues were selected to verify the expression of UHRF1 in MPM and non-cancerous pleural tissues by RT-qPCR. The results of the bioinformatics analysis showed that the expression of UHRF1 in MPM tissues was significantly higher than that in lung tissues, and the patients with high UHRF1 expression levels were relatively worse in prognosis (P < 0.01). The expression of gene UHRF1 is significantly correlated with the infiltration levels of various immune cells such as CD4⁺helper T cell-2, CD4⁺effector memory T cells, macrophages, etc. (P < 0.01). Functional enrichment analysis showed that UHRF1 mainly played a role in DNA replication, proteasome, homologous recombination and other pathways. In the collected cases. the expression of UHRF1 was significantly higher in MPM compared with non-cancerous pleural tissues (P < 0.001). UHRF1 may affect the prognosis of MPM patients through DNA methylation regulation and immune cell infiltration, and is expected to be a potential target for MPM prognosis evaluation.