Pan-cancer analysis shows that TNFSF4 is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including liver cancer.

IF 3.4 2区医学 Q2 ONCOLOGY

BMC Cancer Pub Date : 2025-01-17 DOI:10.1186/s12885-025-13479-4

Zhaoda Deng, Lincheng Li, Zihe Meng, Guineng Zeng, Rui Cao, Rong Liu

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引用次数: 0

Abstract

Background: As a member of the tumor necrosis factor (TNF) superfamily, tumor necrosis factor superfamily member 4 (TNFSF4) is expressed on antigen-presenting cells and activated T cells by binding to its receptor TNFRSF4. However, tumorigenicity of TNFSF4 has not been studied in pan-cancer. Therefore, comprehensive bioinformatics analysis of pan-cancer was performed to determine the mechanisms through which TNFSF4 regulates tumorigenesis.

Methods: RNA-seq data for 33 cancers were analyzed from UCSC XENA database. Online websites and databases were used to investigate TNFSF4's biological function, epigenetic modifications, genetic alterations, and tumor immunity. Furthermore, cell phenotype experiment and tumor xenotransplantation experiment were performed to determine the biological functions of TNFSF4.

Results: The pan-cancer analysis showed that TNFSF4 was upregulated in several tumors. Significant relationships between TNFSF4 expression and single-cells data were also observed in numerous cancer types. TNFSF4 expression correlated with the expression of immune checkpoint genes and could influence various drug sensitivity. Vitro and vivo experiments showed that TNFSF4 could promote the development and progression of Hepatocellular Carcinoma (HCC).

Conclusions: TNFSF4 was upregulated in multiple cancer types and promoted the development and progression of cancers through several mechanisms including regulation of the tumor-infiltration of immune cells. Our study shows that TNFSF4 is a promising prognostic and immunotherapeutic biomarker in some malignant tumors.

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泛癌症分析表明，TNFSF4是包括肝癌在内的多种癌症类型的潜在预后和免疫治疗生物标志物。

背景：肿瘤坏死因子超家族成员4 （tumor necrosis factor superfamily member 4, TNFSF4）作为肿瘤坏死因子（TNF）超家族的一员，通过与其受体TNFRSF4结合在抗原呈递细胞上表达并激活T细胞。然而，TNFSF4在泛癌中的致瘤性尚未得到研究。因此，我们对泛癌进行了全面的生物信息学分析，以确定TNFSF4调控肿瘤发生的机制。方法：对UCSC XENA数据库中33例肿瘤的RNA-seq数据进行分析。利用在线网站和数据库研究TNFSF4的生物学功能、表观遗传修饰、遗传改变和肿瘤免疫。此外，通过细胞表型实验和肿瘤异种移植实验来确定TNFSF4的生物学功能。结果：泛癌分析显示，TNFSF4在多种肿瘤中表达上调。在许多癌症类型中也观察到TNFSF4表达与单细胞数据之间的显著关系。TNFSF4表达与免疫检查点基因表达相关，可影响多种药物敏感性。体外和体内实验表明，TNFSF4可促进肝细胞癌（HCC）的发生和进展。结论：TNFSF4在多种癌症类型中表达上调，并通过调节免疫细胞的肿瘤浸润等多种机制促进癌症的发生和进展。我们的研究表明，TNFSF4在某些恶性肿瘤中是一种有前景的预后和免疫治疗生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Cancer 医学-肿瘤学

CiteScore

6.00

自引率

2.60%

发文量

1204

审稿时长

6.8 months

期刊介绍： BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.