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PD-L1 与肝细胞癌中 mA RNA 甲基化调节剂及其 miRNA 调节剂的免疫浸润。

PD-L1 and Immune Infiltration of mA RNA Methylation Regulators and Its miRNA Regulators in Hepatocellular Carcinoma.

机构信息

Department of Medicine, Affiliated Hospital of Chengde Medical University, Nanyingzi Road, Shuangqiao District, Chengde, Hebei, China.

Department of Pathophysiology, Chengde Medical University, Anyuan Road, Shuangqiao District, Chengde, Hebei, China.

出版信息

Biomed Res Int. 2021 May 15;2021:5516100. doi: 10.1155/2021/5516100. eCollection 2021.

Abstract

BACKGROUND

The aim of this study was to systematically evaluate the relationship between the expression of mA RNA methylation regulators and prognosis in HCC.

METHODS

We compared the expression of mA methylation modulators and PD-L1 between HCC and normal in TCGA database. HCC samples were divided into two subtypes by consensus clustering of data from mA RNA methylation regulators. The differences in PD-L1, immune infiltration, and prognosis between the two subtypes were further compared. The LASSO regression was used to build a risk score for mA modulators. In addition, we identified miRNAs that regulate mA regulators.

RESULTS

We found that fourteen mA regulatory genes were significantly differentially expressed between HCC and normal. HCC samples were divided into two clusters. Of these, there are higher PD-L1 expression and poorer overall survival (OS) in cluster 1. There was a significant difference in immune cell infiltration between cluster 1 and cluster 2. Through the LASSO model, we obtained 12 mA methylation regulators to construct a prognostic risk score. Compared with patients with a high-risk score, patients with a low-risk score had upregulated PD-L1 expression and worse prognosis. There was a significant correlation between risk score and tumor-infiltrating immune cells. Finally, we found that miR-142 may be the important regulator for mA RNA methylation in HCC.

CONCLUSION

Our results suggest that mA RNA methylation modulators may affect the prognosis through PD-L1 and immune cell infiltration in HCC patients. In addition, the two clusters may be beneficial for prognostic stratification and improving immunotherapeutic efficacy.

摘要

背景

本研究旨在系统评估 mA RNA 甲基化调节剂的表达与 HCC 预后之间的关系。

方法

我们比较了 TCGA 数据库中 HCC 和正常组织中 mA 甲基化调节剂的表达和 PD-L1 水平。根据 mA RNA 甲基化调节剂数据进行共识聚类,将 HCC 样本分为两个亚型。进一步比较两个亚型之间 PD-L1、免疫浸润和预后的差异。使用 LASSO 回归构建 mA 调节剂的风险评分。此外,我们鉴定了调节 mA 调节剂的 miRNA。

结果

我们发现 14 个 mA 调节基因在 HCC 和正常组织之间存在显著差异表达。HCC 样本分为两个簇。其中,簇 1 的 PD-L1 表达更高,总生存期(OS)更差。簇 1 和簇 2 之间的免疫细胞浸润有显著差异。通过 LASSO 模型,我们获得了 12 个 mA 甲基化调节剂来构建预后风险评分。与高风险评分患者相比,低风险评分患者的 PD-L1 表达上调,预后更差。风险评分与肿瘤浸润免疫细胞之间存在显著相关性。最后,我们发现 miR-142 可能是 HCC 中 mA RNA 甲基化的重要调节因子。

结论

我们的研究结果表明,mA RNA 甲基化调节剂可能通过 PD-L1 和免疫细胞浸润影响 HCC 患者的预后。此外,这两个簇可能有助于预后分层和提高免疫治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6cc5/8147529/bbb525dbb1bc/BMRI2021-5516100.001.jpg

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