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上调的 PXDNL 促进浸润性乳腺癌进展

英文原题:Upregulated PXDNL promotes invasive breast carcinoma progression.

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Upregulated PXDNL promotes invasive breast carcinoma progression.

PubMed 2025/03/15(内容时间) Am J Transl Res Q3 · IF 1.8(JCR 2025)

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研究概要

PXDNL 过表达与 BRCA 不良预后相关,并与免疫细胞浸润有关。因此,PXDNL 可能作为 BRCA 的生物标志物或治疗靶点。

研究思路结论见上方概要

侵袭性乳腺癌(BRCA)是女性常见且严重的恶性肿瘤。过氧化物酶样蛋白(PXDNL)与多种癌症的不良预后相关,但其在BRCA进展中的作用尚不明确。

对来自癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)和UALCAN的数据集进行生物信息学分析,探讨PXDNL的潜在致癌作用,重点关注其与预后、启动子甲基化、免疫细胞浸润、免疫检查点基因以及相关生物学功能和通路的相关性。

PXDNL在BRCA中表现出显著的表达谱,具有重要的诊断和预后意义。其上调与BRCA各种分子亚型中生存率降低相关。PXDNL高表达组患者中多种浸润性免疫细胞类型的存在减少,包括CD8+ T细胞、细胞毒性细胞、T细胞、B细胞、树突状细胞(DC)、未成熟树突状细胞(iDC)、自然杀伤(NK)细胞、NK CD56bright细胞、NK CD56dim细胞和滤泡辅助性T细胞(TFH)。此外,观察到PXDNL表达与免疫检查点基因之间存在显著相关性。基因集富集分析(GSEA)进一步表明,PXDNL高表达触发上皮-间质转化和蛋白质分泌等通路,同时抑制包括同种异体移植排斥、IL6-JAK-STAT3信号传导、通过NFκB的TNFα信号传导、脂肪生成、氧化磷酸化、DNA修复和P53通路在内的关键过程。

展开英文摘要原文

Invasive breast carcinoma (BRCA) is a common and serious malignancy in women. Peroxidase-like (PXDNL) is associated with poor prognosis in various cancers but has an unclear role in BRCA progression.

Bioinformatic analysis of datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and UALCAN investigated a potential carcinogenic role of PXDNL, focusing on its correlation with prognosis, promoter methylation, immune cell infiltration, immune checkpoint genes, and relevant biologic functions and pathways.

PXDNL demonstrated a significant expression profile in BRCA, with considerable diagnostic and prognostic implications. Its up-regulation correlated with decreased survival rates across various molecular subtypes of BRCA. Patients in the high PXDNL expression group showed reduced presence of multiple infiltrative immune cell types, including CD8+ T cells, cytotoxic cells, T cells, B cells, dendritic cells (DC), immature dendritic cells (iDC), natural killer (NK) cells, NK CD56bright cells, NK CD56dim cells, and follicular helper T cells (TFH). Additionally, a significant correlation was observed between PXDNL expression and immune checkpoint genes. Gene Set Enrichment Analysis (GSEA) further indicated that high PXDNL expression triggers pathways such as epithelial-mesenchymal transition and protein secretion, while suppressing crucial processes including allograft rejection, IL6-JAK-STAT3 signaling, TNFα signaling via NFκB, adipogenesis, oxidative phosphorylation, DNA repair, and the P53 pathway.

Overexpression of PXDNL is associated with poor prognosis and is linked to immune cell infiltration in BRCA. Thus, PXDNL may be a biomarker or therapeutic target for BRCA.

论文信息

作者
Zhou X、Zhang Y、Huang B、Shi X、Bian M
单位
Department of Blood Transfusion, The First Affiliated Hospital of Anhui Medical University Hefei, Anhui, The People's Republic of China.China
期刊
American journal of translational research2025
原文标识
PubMed 40225987 · DOI 10.62347/BOUC4040