Yuanguang Meng

4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

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.