Integrative analysis and experiment validation of SLC12A8 as a biomarker for the malignant transition from endometriosis to endometriosis associated ovarian cancer

Dou Y, Yingyu Dou, Bairong Xia, Xia B
Functional & integrative genomics · 2026 · vol. 26(1) · doi:10.1007/s10142-026-02047-z · PMID:42742760 · W7213319413
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Abstract

Endometriosis (EM) is a chronic inflammatory, estrogen‑dependent benign gynecological disorder. A subset of patients with EM may subsequently develop endometriosis‑associated ovarian cancer (EAOC), implying a biological continuum between these two conditions. Nevertheless, the molecular events underlying the progression from benign endometriotic lesions toward EAOC remain incompletely characterized. In this study, transcriptomic datasets retrieved from the GEO database were interrogated through differentially expressed gene screening, functional enrichment analysis, and weighted gene co‑expression network analysis (WGCNA) to identify key genes and pathways relevant to EM and EAOC. Candidate genes were further prioritized by integrating survival analysis via the Kaplan‑Meier Plotter, LASSO regression, random‑forest modeling, and CIBERSORT immune‑infiltration profiling. Loss and gain‑of‑function cellular models were established using siRNA and overexpression plasmids, and in‑vitro functional assays were performed to characterize the phenotypic effects of target genes.We identified several candidate genes associated with EM and EAOC and evaluated their discriminatory performance. Among them, SLC12A8 elevated expression across EM and EAOC tissues and exhibited moderate diagnostic capacity. Higher SLC12A8 expression was also associated with poorer prognosis in EAOC patients. In‑vitro experiments further demonstrated that SLC12A8 modulates proliferation, invasion, and migration in both EM and EAOC cell lines. Collectively, our exploratory research findings support SLC12A8 as a candidate functional mediator and potential biomarker linked to EM‑EAOC pathological progression, thereby extending the mechanistic understanding of these disorders.

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MeSH descriptors

Biomarkers, Tumor Biomarkers, Tumor Biomarkers, Tumor Biomarkers, Tumor Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Solute Carrier Family 12 Solute Carrier Family 12 Cell Movement Cell Movement

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