Upregulated PXDNL promotes invasive breast carcinoma progression

PXDNL 上调促进浸润性乳腺癌进展

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Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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