DPT has potential to be a prognostic biomarker and its correlation with immune infiltrates in prostate cancer.

IF 1.3 Q4 IMMUNOLOGY
American journal of clinical and experimental immunology Pub Date : 2025-08-15 eCollection Date: 2025-01-01 DOI:10.62347/BTHG8733
Jieyu Jin, Junchao Feng, Tong Zhou, Jun Cao, Bin Feng, Qingqin Tang, Sheng Zhang, Jun Qiu, Yuting Liang
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Abstract

Background: Prostate cancer (PRAD) poses a significant threat to male health. The tumor microenvironment (TME) plays a crucial role in its development process, yet the regulatory significance of specific extracellular matrix proteins such as Dermatopontin (DPT) in PRAD remains poorly understood.

Methods: A total of 534 PRAD transcriptome profiles were retrieved from The Cancer Genome Atlas (TCGA) database. CIBERSORT and ESTIMATE computational methods were used to quantify the presence of immune and stromal components. Differentially expressed genes (DEGs) were identified based on ImmuneScore and StromalScore, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genomes (KEGG) pathway enrichment analyses. DPT expression was analyzed in relation to overall survival, TNM staging, immune-related pathways using Gene Set Enrichment Analysis (GSEA), and tumor-infiltrating immune cells (TICs).

Results: A total of 454 DEGs overlapping between high ImmuneScore and StromalScore groups were enriched in immune-related processes and pathways. DPT expression was positively correlated with the survival of PRAD patients, especially the N Stage of PRAD. GSEA revealed that high DPT expression correlated with immune-related activities such as allograft rejection, apical junction, complement, and epithelial mesenchymal transition while low DPT expression was correlated with metabolic pathways such as E2f targets, G2m checkpoint, mitotic spindle, and mitorc1 signaling. Analysis of TICs showed that DPT expression was positively correlated with resting mast cells and neutrophils. Conversely, regulatory T cells, M1 macrophages, M2 macrophages, and resting dendritic cells exhibited negative correlations with DPT expression.

Conclusions: DPT may serve as a novel prognostic biomarker in PRAD, potentially affecting the survival of PRAD patients by regulating the immune environment of TME. These findings provide new insights into the immunomodulatory role of DPT and its potential as a therapeutic target for PRAD.

DPT有可能成为前列腺癌的预后生物标志物及其与免疫浸润的相关性。
背景:前列腺癌(PRAD)对男性健康构成重大威胁。肿瘤微环境(tumor microenvironment, TME)在PRAD的发展过程中起着至关重要的作用,但特异性细胞外基质蛋白如皮肤桥蛋白(Dermatopontin, DPT)在PRAD中的调控作用尚不清楚。方法:从癌症基因组图谱(TCGA)数据库中检索534个PRAD转录组图谱。使用CIBERSORT和ESTIMATE计算方法量化免疫和基质成分的存在。基于ImmuneScore和StromalScore对差异表达基因(DEGs)进行鉴定,随后进行基因本体(GO)和京都基因组百科全书(KEGG)途径富集分析。使用基因集富集分析(GSEA)分析DPT表达与总生存率、TNM分期、免疫相关途径和肿瘤浸润免疫细胞(TICs)的关系。结果:在免疫相关的过程和途径中,高免疫评分组和StromalScore组之间共有454度重叠。DPT的表达与PRAD患者的生存呈正相关,尤其是在PRAD的N期。GSEA显示,DPT高表达与免疫相关活动相关,如异体移植物排斥反应、根尖连接、补体和上皮间质转化,而DPT低表达与代谢途径相关,如E2f靶点、G2m检查点、有丝分裂纺锤体和mitorc1信号传导。tic分析显示,DPT的表达与静止肥大细胞和中性粒细胞呈正相关。相反,调节性T细胞、M1巨噬细胞、M2巨噬细胞和静息树突状细胞与DPT表达呈负相关。结论:DPT可能作为一种新的PRAD预后生物标志物,可能通过调节TME的免疫环境影响PRAD患者的生存。这些发现为DPT的免疫调节作用及其作为PRAD治疗靶点的潜力提供了新的见解。
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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