tRNA甲基转移酶1在前列腺癌组织中的表达及其与免疫细胞浸润的相关性

Expression of TRMT1 in prostate cancer tissues and its correlation with immune cell infiltration

目的:利用多种生物信息数据库和免疫组化分析tRNA甲基转移酶1(tRNA methyltransferase 1,TRMT1)在前列腺癌(prostate cancer,PCa)组织中的表达及其与免疫细胞浸润的相关性。方法:利用UALCAN数据库分析TRMT1 mRNA在PCa组织和正常前列腺组织中的表达差异;收集2019年01月至2021年06月在我院泌尿外科行手术治疗的52例PCa患者和20例前列腺增生(benign prostatic hyperplasia,BPH)患者的组织石蜡切片,使用免疫组化的方法分析TRMT1蛋白在PCa和BPH组织中的表达差异;结合免疫组化结果和临床病理资料,分析TRMT1蛋白的表达与PCa患者临床病理特征的相关性;利用LinkedOmics数据库检索与TRMT1相关的共表达基因,并使用Metascape数据库进行富集分析;利用String数据库构建TRMT1蛋白互作网络;利用TIMER2.0数据库分析TRMT1的表达与免疫细胞浸润的相关性;利用GEPIA数据库分析TRMT1的表达与PCa患者预后的相关性。结果:与正常前列腺组织相比,TRMT1 mRNA在PCa组织中的表达显著增加(P<0.05)。免疫组化结果显示,TRMT1蛋白在PCa组织中的表达显著高于BPH组织(P<0.05)。TRMT1的表达与PCa患者的Gleason评分有关(P<0.05),而与年龄、术前PSA水平和TNM分期无关(P>0.05)。富集分析结果显示,TRMT1相关基因主要与RNA代谢和RNA加工修饰等相关。TRMT1的表达与CD8^(+)T细胞、CD4^(+)T细胞、B细胞、中性粒细胞、巨噬细胞和骨髓树突状细胞的免疫细胞浸润水平呈负相关。在PCa患者中,TRMT1高表达组的总生存期(overall survival,OS)和无病生存期(disease free survival,DFS)要明显低于TRMT1低表达组(P<0.05)。结论:TRMT1在PCa中高表达,参与调节免疫细胞浸润,与PCa患者的不良预后相关,可能成为PCa诊断、治疗及判断预后的新的生物标志物。

Objective:To analyze the expression of tRNA methyltransferase 1(TRMT1)in prostate cancer(PCa)tissues and its correlation with immune cell infiltration based on multiple bioinformatic databases and immunohistochemistry.Methods:The differential expressions of TRMT1 mRNA in PCa tissues and normal prostate tissues were analyzed by using UALCAN database.The paraffin-embedded specimens of 52 patients with PCa and 20 patients with benign prostatic hyperplasia(BPH)who underwent surgery in the department of urology of our hospital from January 2019 to June 2021 were collected.The differential expression of TRMT1 protein in PCa and BPH tissues was analyzed by immunohistochemistry.The correlation between the expression of TRMT1 protein and the clinicopathological characteristics of PCa patients was analyzed according to the results of immunohistochemistry and clinical medical records.The LinkedOmics database was used to search for co-expressed genes associated with TRMT1,and the Metascape database was used for enrichment analysis.The TRMT1 protein-protein interaction network was constructed by String database.The correlation between TRMT1 expression and immune cell infiltration was analyzed by TIMER2.0 database.The correlation between TRMT1 expression and prognosis of PCa patients was analyzed by GEPIA database.Results:Compared with normal prostate tissues,the expression of TRMT1 mRNA was higher in PCa tissues(P<0.05).Immunohistochemical results showed that the expression of TRMT1 protein in PCa tissues was significantly higher than that in BPH tissues(P<0.05).The expression of TRMT1 was correlated with the Gleason score of PCa patients(P<0.05),but not with age,preoperative PSA level and TNM stage(P>0.05).The results of enrichment analysis showed that TRMT1-related genes were mainly related to RNA metabolism and RNA modification.The expression of TRMT1 was negatively correlated with the level of immune cell infiltration of CD8^(+)T cells,CD4^(+)T cells,B cells,neutrophils,macrophages and myeloid dendritic cells.In PCa patients,the overall survival(OS)and disease free survival(DFS)of TRMT1 high expression group were significantly lower than those of TRMT1 low expression group(P<0.05).Conclusion:TRMT1 is highly expressed in PCa and is involved in the regulation of immune cell infiltration,which is associated with poor prognosis of PCa patients and may become a new biomarker for PCa diagnosis,treatment and prognosis.