AUTHOR=Li Yingxiao , Chen Haoyue , Zhang Hao , Lin Zhaochen , Song Liang , Zhao Chuanliang 

TITLE=Identification of oxidative stress-related biomarkers in uterine leiomyoma: a transcriptome-combined Mendelian randomization analysis

JOURNAL=Frontiers in Endocrinology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1373011

DOI=10.3389/fendo.2024.1373011

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>Oxidative stress has been implicated in the pathogenesis of uterine leiomyoma (ULM) with an increasing incidence. This study aimed to identify potential oxidative stress-related biomarkers in ULM using transcriptome data integrated with Mendelian randomization (MR) analysis.</p></sec><sec><title>Methods</title><p>Data from GSE64763 and GSE31699 in the Gene Expression Omnibus (GEO) were included in the analysis. Oxidative stress-related genes (OSRGs) were identified, and the intersection of differentially expressed genes (DEGs), Weighted Gene Co-expression Network Analysis (WGCNA) genes, and OSRGs was used to derive differentially expressed oxidative stress-related genes (DE-OSRGs). Biomarkers were subsequently identified <italic>via</italic> MR analysis, followed by Gene Set Enrichment Analysis (GSEA) and immune infiltration analysis. Nomograms, regulatory networks, and gene-drug interaction networks were constructed based on the identified biomarkers.</p></sec><sec><title>Results</title><p>A total of 883 DEGs were identified between ULM and control samples, from which 42 DE-OSRGs were screened. MR analysis revealed four biomarkers: <italic>ANXA1</italic>, <italic>CD36</italic>, <italic>MICB</italic>, and <italic>PRDX6</italic>. Predictive nomograms were generated based on these biomarkers. <italic>ANXA1</italic>, <italic>CD36</italic>, and <italic>MICB</italic> were significantly enriched in chemokine signaling and other pathways. Notably, <italic>ANXA1</italic> showed strong associations with follicular helper T cells, resting mast cells, and M0 macrophages. <italic>CD36</italic> was positively correlated with resting mast cells, while <italic>MICB</italic> was negatively correlated with macrophages. Additionally, <italic>ANXA1</italic> displayed strong binding energy with amcinonide, and <italic>MICB</italic> with ribavirin.</p></sec><sec><title>Conclusion</title><p>This study identified oxidative stress-related biomarkers (ANXA1, CD36, MICB, and PRDX6) in ULM through transcriptomic and MR analysis, providing valuable insights for ULM therapeutic research.</p></sec>