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ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1580622
This article is part of the Research Topic Integrative Multi-Omics Approaches for Predicting Immunotherapy Efficacy in Solid Tumors View all 3 articles
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Background: Breast cancer (BRCA) is a significant threat to women's health worldwide, and its progression is closely associated with the tumor microenvironment and gene regulation. Lactylation modification, as a key epigenetic mechanism in cancer biology, has not yet been fully elucidated in the context of BRCA. This study examines the regulatory mechanisms of lactylation-related genes (LRGs), specifically PRDX1, and their prognostic significance in BRCA.We integrated data from multiple databases, including Genome-Wide Association Study (GWAS) summary statistics, single-cell RNA sequencing, spatial transcriptomics, and bulk RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using Summary-based Mendelian Randomization (SMR) analysis, we identified LRGs associated with BRCA and comprehensively analysed the expression patterns of PRDX1, cell-cell communication networks, and spatial heterogeneity. Furthermore, we constructed and validated a prognostic model based on the gene expression profile of PRDX1-positive monocytes, evaluating it through Cox regression and LASSO regression analyses.Results: PRDX1 was identified as a key LRG significantly associated with BRCA risk (p_SMR = 0.0026). Single-cell RNA sequencing analysis revealed a significant upregulation of PRDX1 expression in monocytes, with enhanced cell-cell communication between PRDX1-positive monocytes and fibroblasts. Spatial transcriptomics analysis uncovered heterogeneous expression of PRDX1 in the tumor nest regions, highlighting the spatial interaction between PRDX1-positive monocytes and fibroblasts. The prognostic model constructed based on the gene expression profile of PRDX1-positive monocytes demonstrated high accuracy in predicting patient survival in both the training and validation cohorts. High-risk patients exhibited immune-suppressive microenvironment characteristics, including reduced immune cell infiltration and upregulation of immune checkpoint gene expression.This study reveals the key role of PRDX1 in BRCA progression, mainly through the regulation of the tumor microenvironment and immune escape mechanisms. The survival prediction model based on PRDX1 shows robust prognostic potential, and future research should focus on integrating PRDX1 with other biomarkers to enhance the precision of personalised medicine.
Keywords: breast cancer, Prdx1, lactylation, Spatial transcriptomics, prognostic model 1
Received: 20 Feb 2025; Accepted: 20 Mar 2025.
Copyright: © 2025 Wu, Cao, Jin, Ma, Niu, Yu, Xiang and Xia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yiqin Xia, Nanjing Medical University, Nanjing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
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