Integrated analysis of polytranscriptomics reveals TNFSF ligand genes in pancreatic cancer prognosis and immune regulation.

IF 2.9 4区 医学 Q3 IMMUNOLOGY
Zhaoda Deng, Lincheng Li, Zitong Yang, Guineng Zeng, Rong Liu
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引用次数: 0

Abstract

The tumor necrosis factor (TNF) ligand superfamily plays a critical role in immune regulation and has emerged as a promising target in cancer immunotherapy. By binding to its receptor OX40 (CD134), TNFSF4 promotes the proliferation and survival of T cells and plays an important role in the tumor immune microenvironment, but its role in pancreatic cancer is unclear. This study aimed to investigate the expression patterns and prognostic significance of TNF ligand family members in pancreatic cancer (PC), with a specific focus on TNFSF4. We analyzed single-cell RNA sequencing data from the GSE212966 dataset to assess the expression of TNFSF ligands across immune cell types. TCGA-PAAD bulk RNA-seq data were used for non-negative matrix factorization (NMF) clustering to identify molecular subtypes based on TNFSF ligand expression profiles. Immune infiltration was quantified using single-sample gene set enrichment analysis (ssGSEA), and Kaplan-Meier survival curves were used to compare overall survival (OS) and progression-free survival (PFS) between subtypes. Immunotherapy response prediction was evaluated using tumor mutational burden (TMB), immunophenoscore (IPS), and tumor immune dysfunction and exclusion (TIDE) scores. Gene expression validation was performed using qRT-PCR. TNFSF ligands were predominantly expressed in antigen-presenting cells, particularly B cells and macrophages. NMF clustering identified two molecular subtypes of PC, with cluster 2 associated with significantly better OS and PFS (p < 0.05). TNFSF4, highly enriched in B cells, was found to regulate immune-related pathways such as B cell receptor signaling and cytokine-cytokine receptor interaction, as revealed by KEGG pathway analysis. TNFSF4 expression also correlated with favorable immunotherapy markers, suggesting its potential role as a predictive biomarker. These findings were supported by qRT-PCR validation. This study provides a TNFSF ligand-based molecular classification of pancreatic cancer and highlights the immunoregulatory role of TNFSF4. Its association with patient prognosis and immunotherapy responsiveness suggests potential clinical utility in guiding treatment strategies.

多转录组学综合分析揭示TNFSF配体基因在胰腺癌预后和免疫调节中的作用。
肿瘤坏死因子(TNF)配体超家族在免疫调节中起着至关重要的作用,已成为癌症免疫治疗的一个有希望的靶点。TNFSF4通过与其受体OX40 (CD134)结合,促进T细胞增殖和存活,并在肿瘤免疫微环境中发挥重要作用,但其在胰腺癌中的作用尚不清楚。本研究旨在探讨TNF配体家族成员在胰腺癌(PC)中的表达模式及其预后意义,并特别关注TNFSF4。我们分析了来自GSE212966数据集的单细胞RNA测序数据,以评估TNFSF配体在免疫细胞类型中的表达。TCGA-PAAD散装RNA-seq数据用于非负矩阵因子分解(NMF)聚类,以TNFSF配体表达谱为基础鉴定分子亚型。采用单样本基因集富集分析(ssGSEA)定量免疫浸润,采用Kaplan-Meier生存曲线比较各亚型的总生存期(OS)和无进展生存期(PFS)。使用肿瘤突变负担(TMB)、免疫表型评分(IPS)和肿瘤免疫功能障碍和排斥(TIDE)评分评估免疫治疗反应预测。采用qRT-PCR进行基因表达验证。tnf - sf配体主要表达于抗原呈递细胞,尤其是B细胞和巨噬细胞。NMF聚类鉴定出两种PC分子亚型,其中聚类2与更好的OS和PFS相关
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来源期刊
BMC Immunology
BMC Immunology 医学-免疫学
CiteScore
5.50
自引率
0.00%
发文量
54
审稿时长
1 months
期刊介绍: BMC Immunology is an open access journal publishing original peer-reviewed research articles in molecular, cellular, tissue-level, organismal, functional, and developmental aspects of the immune system as well as clinical studies and animal models of human diseases.
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