FCGR2B
+
Macrophages as a Critical Node Linking Ferroptosis and Immunosuppression: A Multiomics Framework for Prognosis and Therapy in High‐Grade Serous Ovarian Cancer
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.
