Multi-omics Approaches for Biomarker Discovery of Uterine Fibroids: A Systematic Review

Uterine fibroids are the most common benign gynecological tumors, affecting up to 70-80% of women, yet still lack clinically validated biomarkers for disease stratification, monitoring, or therapeutic targeting. Advances in multi-omics technologies offer unprecedented opportunities for biomarker discovery; however, their application in fibroid research remains fragmented across platforms, biological samples, and study designs, limiting translational progress.

The PubMed, Embase, and Scopus databases were searched from 2000 to July 15, 2025, to identify relevant studies. Original, peer-reviewed articles using high-throughput omics technologies to discover fibroid-associated biomarkers were included. A narrative synthesis approach was employed to summarize the findings of included studies and map candidate biomarkers to their biological pathways. The methodological quality of the studies was assessed using the QUADOMICS tool. The protocol of this review was registered in PROSPERO platform (registration number CRD420251125813).

Thirty‑two studies met the inclusion criteria, including genomics (n = 10, 31.3%), transcriptomics (n = 8, 25.0%), epigenomics (n = 3, 9.4%), proteomics (n = 4, 12.5%), metabolomics (n = 3, 9.4%), and multi‑omics (n = 4, 12.5%) approaches for biomarker discovery of uterine fibroids. Single‑omics designs predominated (87.5%) over integrated multi‑omics (12.5%). Six convergent pathways emerged across the different omics layers-extracellular matrix remodeling, hormone signaling, cell cycle regulation, apoptosis resistance, oxidative stress/metabolism, and genome stability-anchored by recurrent biomarker candidates.

This review provides the first systematic synthesis of high-throughput omics-based biomarker discovery in uterine fibroids across multiple biological samples. The convergence of multi‑omics findings on a small set of interconnected pathways supports the view of fibroids as a systems‑level disease and highlights tractable molecular targets that could inform non‑invasive biomarker panels and guide the translation of new pathway‑directed therapeutics beyond surgery. Critical gaps still include insufficient utilization of non-invasive samples, limited integration of multi-omics data, and inconsistent validation. Future research requires large-scale, integrated approaches that prioritize circulating biomarkers for clinical translation.