Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40861438", "kind": "science-record", "revision": 4, "content_hash": "sha256:61a24dbb36192880879ba343db272ba3635c7a1b73e5b30f8b057b35eb00f428", "created_at": "2026-11-01T20:30:59Z", "updated_at": "2026-11-01T22:57:06Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas.", "doi": "10.3389/fimmu.2025.1627057", "pmid": "40861438", "authors": ["Qianghua Wang", "Xuegu Wang", "Jiaojiao Fei", "Chuanyue Jiang", "Yafen Tao", "Nana Yang", "Huijuan Chen", "Chengli Dou", "Biao Ding", "Danli Du", "Xiang Li"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: Early-onset preeclampsia (EOPE) is a severe form of preeclampsia that mainly contributes to maternal and perinatal morbidity and mortality worldwide. This study aimed to systematically analyze the expression and function of ferroptosis-related gene HILPDA in EOPE placentas.\nMethods: We included five transcriptomic datasets (GSE148241, GSE44711, GSE74341, GSE114691, GSE10588) downloaded from the Gene Expression Omnibus (GEO) in this study. Using differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning models (LASSO, SVM-RFE, Random Forest), We identified hub genes and diagnostic biomarkers. We performed functional enrichment (GO and KEGG) and immune infiltration analysis to elucidate molecular mechanisms. Experimental validation included Western blot on clinical placental samples and siRNA-mediated knockdown in HTR-8/SVneo trophoblasts to assess migration.\nResults: We observed HILPDA upregulation and confirmed its diagnostic accuracy (AUC=0.71) in EOPE placentas. Functional analysis revealed HILPDA-associated enrichment in immune regulation (leukocyte migration, MHC complexes) and cellular processes (collagen organization, HIF-1 signaling). Through WGCNA, we identified 171 HILPDA-associated DEGs. Machine learning prioritized PART1 as diagnostic biomarkers. Immune profiling highlighted HILPDA's correlation with activated dendritic cells, neutrophils and resting mast cells. Experimentally, we confirmed HILPDA up-regulation in EOPE placentas and its critical role in suppressing trophoblast migration.\nConclusions: Our study establishes HILPDA as a central mechanistic regulator involved in placental immune dysregulation and trophoblast migration in EOPE pathogenesis. The identified biomarkers PART1 and HILPDA-associated pathways may offer novel diagnostic and therapeutic targets for EOPE management, which contribute to reduce maternal morbidity and prevent perinatal mortality in this catastrophic pregnancy syndrome.", "claims": [{"id": "claim-method", "statement": "The limma and DESeq2 packages in R were used to identify differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40861438", "locator": "sections[9] \"Differentially expressed genes analysis and the screening and evaluation of candidate genes\" paragraph 2", "quote": "The limma and DESeq2 packages in R were used to identify differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40861438", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/ Supplementary Material . 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