Hum Mutat. 2026 Apr 6;2026:8027584. doi: 10.1155/humu/8027584. eCollection 2026.

ABSTRACT

BACKGROUND: High-grade serous ovarian cancer (HGSOC) is characterized by a complex tumor microenvironment and poor prognosis, yet the roles of specific tumor-associated macrophages (TAMs) subpopulations in driving disease progression remain elusive.

METHODS: This study evaluated the prognostic relevance of FCGR2B in HGSOC. Single-cell RNA sequencing identified FCGR2B ⁺ TAMs as a distinct macrophage subpopulation with unique transcriptional features. Integrative analyses combining single-cell and bulk differentially expressed genes, macrophage-associated modules, and ferroptosis-related gene sets identified 26 candidate prognostic genes, from which a four-gene signature (CRYAB, PLAUR, EREG, and C5AR1) was derived to construct the prognostic risk model. The model was validated in an independent cohort. Immune infiltration, single-cell trajectory, copy number variation, and drug-gene associations were analyzed to explore the molecular and therapeutic implications of risk stratification.

RESULTS: HGSOC patients classified as high risk exhibited poorer survival outcomes, increased infiltration of M2-like macrophages, elevated expression of immune checkpoints, and enrichment of immune- and ferroptosis-related pathways. Trajectory and copy number variation analyses revealed stage-specific gene expression patterns and amplification-associated regulation. Drug-gene association analyses further suggested that high-risk patients may be more responsive to targeted therapies and proteasome inhibitors, whereas low-risk patients may benefit from conventional chemotherapy.

CONCLUSION: FCGR2B ⁺ TAMs are closely linked to HGSOC progression, and the proposed prognostic model based on FCGR2B ⁺ TAMs provides predictive value and potential therapeutic insights for patient stratification.

PMID:41953398 | PMC:PMC13054137 | DOI:10.1155/humu/8027584