基于公共数据库的单细胞测序分析和加权共表达网络分析构建葡萄膜黑色素瘤的坏死相关预后模型。

A Necroptosis-Related Prognostic Model of Uveal Melanoma Was Constructed by Single-Cell Sequencing Analysis and Weighted Co-Expression Network Analysis Based on Public Databases.

机构信息

Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.

Department of General Surgery, Fuyang Hospital Affiliated to Anhui Medical University, Fuyang, China.

出版信息

Front Immunol. 2022 Feb 15;13:847624. doi: 10.3389/fimmu.2022.847624. eCollection 2022.

DOI:10.3389/fimmu.2022.847624

PMID:35242144

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8886618/

Abstract

BACKGROUND

Uveal melanoma(UVM) is the most common intraocular malignancy and has a poor prognosis. The clinical significance of necroptosis(NCPS) in UVM is unclear.

METHODS

We first identified necroptosis genes in UVM by single-cell analysis of the GSE139829 dataset from the GEO database and weighted co-expression network analysis of TCGA data. COX regression and Lasso regression were used to construct the prognostic model. Then survival analysis, immune microenvironment analysis, and mutation analysis were carried out. Finally, cell experiments were performed to verify the role of ITPA in UVM.

RESULT

By necroptosis-related prognostic model, UVM patients in both TCGA and GEO cohorts could be classified as high-NCPS and low-NCPS groups, with significant differences in survival time between the two groups (P<0.001). Besides, the high-NCPS group had higher levels of immune checkpoint-related gene expression, suggesting that they might be more likely to benefit from immunotherapy. The cell experiments confirmed the role of ITPA, the most significant gene in the model, in UVM. After ITPA was knocked down, the activity, proliferation, and invasion ability of the MuM-2B cell line were significantly reduced.

CONCLUSION

Our study can provide a reference for the diagnosis and treatment of patients with UVM.

摘要

背景

葡萄膜黑色素瘤（UVM）是最常见的眼内恶性肿瘤，预后不良。坏死性凋亡（NCPS）在 UVM 中的临床意义尚不清楚。

方法

我们首先通过从 GEO 数据库中的 GSE139829 数据集进行单细胞分析和 TCGA 数据的加权共表达网络分析，鉴定出 UVM 中的坏死性凋亡基因。然后，使用 COX 回归和 Lasso 回归构建预后模型。接下来进行生存分析、免疫微环境分析和突变分析。最后，通过细胞实验验证 ITPA 在 UVM 中的作用。

结果

通过坏死性凋亡相关的预后模型，TCGA 和 GEO 队列中的 UVM 患者可分为高-NCPS 和低-NCPS 组，两组之间的生存时间存在显著差异（P<0.001）。此外，高-NCPS 组中免疫检查点相关基因的表达水平更高，提示它们可能更受益于免疫治疗。细胞实验证实了模型中最显著的基因 ITPA 在 UVM 中的作用。敲低 ITPA 后，MuM-2B 细胞系的活性、增殖和侵袭能力明显降低。