High expression of MRPL52 can be used as a prognostic marker of hepatocellular carcinoma and is related to immune infiltration

Nan HUANG, Xiang LIU, Qichang XING, Jia CHEN, Xiaolan GUO, Wei LI, Zheng LIU
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Abstract

Objective

To analyze the differential expression and prognostic value of Mitochondrial ribosomal protein L52 (MRPL52) in hepatocellular carcinoma using bioinformatics, and to explore the prognostic value and role of the MRPL52 in the immune regulation of hepatocellular carcinoma.

Methods

Hepatocellular Carcinoma Database (HCCDB) and Tumor Immune Estimation Resource (TIMER) databases were used in analyzing the differential expression of MRPL52 in hepatocellular carcinoma tissue and normal paracancerous tissues; UALCAN database was used to analyze the correlation between levels of MRPL52 expression and levels of DNA methylation vs. clinical phenotypes, including tumor grade, tumor stage, and metastasis, Kaplan–Meier plotter database was used in analyzing the relationship between MRPL52 expression and hepatocellular carcinoma survival; LinkedOmics database was used in analyzing MRPL52 co-expression genes, target miRNAs and transcription factors; GENEMANIA database was used to construct the protein interaction network; DiseaseMeth database and MEXPRESS database were used to analyze the level of MRPL52 DNA methylation and changes in methylation sites, and TIMER database was used in analyzing the relationship between MRPL52 and immune infiltration of hepatocellular carcinoma.

Results

MRPL52 was highly expressed in hepatocellular carcinoma and was positively correlated with clinical phenotypes, including tumor grade, tumor stage, and distant metastasis; high expression of MRPL52 was associated with poor prognosis of hepatocellular carcinoma; co-expression analysis showed that MRPL52 co-expression genes were enriched in multiple cancer-related signal pathways, and methylation analysis showed that the DNA methylation level of MRPL52 reduced significantly in hepatocellular carcinoma. Additionally, significant changes were found in methylation sites cg07436208 and cg04556361, which were negatively correlated with the expression level of MRPL52, and K–M survival analysis showed that the cg04556361 methylation site was negatively correlated with the overall survival of hepatocellular carcinoma; MRPL52 was associated with immune cell infiltration of hepatocellular carcinoma, and Cox multivariate regression analysis showed that MRPL52 could increase the risk of overall survival (OS) by 1.435-fold in the absence of immune cells.

Conclusion

The expression level of MRPL52 in patients with hepatocellular carcinoma is increased, which is related closely to poor prognosis, suggesting that MRPL52 is expected to become a prognostic marker and a new target for the treatment of hepatocellular carcinoma.

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MRPL52的高表达可作为肝细胞癌的预后标志物,并与免疫浸润有关
目的应用生物信息学方法分析线粒体核糖体蛋白L52 (MRPL52)在肝细胞癌中的差异表达及预后价值,探讨MRPL52在肝细胞癌免疫调节中的预后价值及作用。方法应用肝细胞癌数据库(HCCDB)和肿瘤免疫估计资源(TIMER)数据库分析MRPL52在肝细胞癌组织和正常癌旁组织中的表达差异;采用UALCAN数据库分析MRPL52表达水平和DNA甲基化水平与临床表型(包括肿瘤分级、肿瘤分期、转移)的相关性,采用Kaplan-Meier绘图图数据库分析MRPL52表达与肝癌存活的关系;利用LinkedOmics数据库分析MRPL52共表达基因、靶mirna和转录因子;利用GENEMANIA数据库构建蛋白相互作用网络;采用disease - emeth数据库和MEXPRESS数据库分析MRPL52 DNA甲基化水平及甲基化位点变化,采用TIMER数据库分析MRPL52与肝癌免疫浸润的关系。结果smrpl52在肝细胞癌中高表达,并与临床表型(肿瘤分级、肿瘤分期、远处转移)呈正相关;MRPL52高表达与肝癌预后不良相关;共表达分析显示,MRPL52共表达基因在多种癌症相关信号通路中富集,甲基化分析显示,MRPL52的DNA甲基化水平在肝细胞癌中显著降低。此外,甲基化位点cg07436208和cg04556361发生显著变化,与MRPL52的表达水平呈负相关,K-M生存分析显示cg04556361甲基化位点与肝细胞癌的总生存呈负相关;MRPL52与肝细胞癌免疫细胞浸润相关,Cox多因素回归分析显示,MRPL52在无免疫细胞情况下可使总生存(OS)风险增加1.435倍。结论MRPL52在肝细胞癌患者中的表达水平升高,与预后不良密切相关,提示MRPL52有望成为肝细胞癌的预后标志物和治疗的新靶点。
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