{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T12:34:39Z","timestamp":1776947679711,"version":"3.51.4"},"reference-count":63,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T00:00:00Z","timestamp":1708041600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Preeclampsia, a severe pregnancy syndrome, is widely accepted divided into early\u2010 and late\u2010onset preeclampsia (EOPE and LOPE) based on the onset time of preeclampsia, with distinct pathophysiological origins. However, the molecular mechanism especially immune\u2010related mechanisms for EOPE and LOPE is currently obscure. In the present study, we focused on placental immune alterations between EOPE and LOPE and search for immune\u2010related biomarkers that could potentially serve as potential therapeutic targets through bioinformatic analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The gene expression profiling data was obtained from the Gene Expression Omnibus database. ESTIMATE algorithm and Gene Set Enrichment Analysis were employed to evaluate the immune status. The intersection of differentially expressed genes in GSE74341 series and immune\u2010related genes set screened differentially expressed immune\u2010related genes. Protein\u2013protein interaction network and random forest were used to identify hub genes with a validation by a quantitative real\u2010time PCR. Kyoto Encyclopedia of Genes and Genomes pathways, Gene Ontology and gene set variation analysis were utilized to conduct biological function and pathway enrichment analyses. Single\u2010sample gene set enrichment analysis and CIBERSORTx tools were employed to calculate the immune cell infiltration score. Correlation analyses were evaluated by Pearson correlation analysis. Hub genes\u2010miRNA network was performed by the NetworkAnalyst online tool.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Immune score and stromal score were all lower in EOPE samples. The immune system\u2010related gene set was significantly downregulated in EOPE compared to LOPE samples. Four hub differentially expressed immune\u2010related genes (<jats:italic>IL15<\/jats:italic>, <jats:italic>GZMB<\/jats:italic>, <jats:italic>IL1B<\/jats:italic> and <jats:italic>CXCL12<\/jats:italic>) were identified based on a protein\u2013protein interaction network and random forest. Quantitative real\u2010time polymerase chain reaction validated the lower expression levels of four hub genes in EOPE compared to LOPE samples. Immune cell infiltration analysis found that innate and adaptive immune cells were apparent lacking in EOPE samples compared to LOPE samples. Cytokine\u2010cytokine receptor, para\u2010inflammation, major histocompatibility complex class I and T cell co\u2010stimulation pathways were significantly deficient and highly correlated with hub genes. We constructed a hub genes\u2010miRNA regulatory network, revealing the correlation between hub genes and hsa\u2010miR\u2010374a\u20105p, hsa\u2010miR\u2010203a\u20103p, hsa\u2010miR\u2010128\u20103p, hsa\u2010miR\u2010155\u20103p, hsa\u2010miR\u2010129\u20102\u20103p and hsa\u2010miR\u20107\u20105p.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The innate and adaptive immune systems were severely impaired in placentas of EOPE. Four immune\u2010related genes (<jats:italic>IL15<\/jats:italic>, <jats:italic>GZMB<\/jats:italic>, <jats:italic>IL1B<\/jats:italic> and <jats:italic>CXCL12<\/jats:italic>) were closely correlated with immune\u2010related pathogenesis of EOPE. The result of our study may provide a new basis for discriminating between EOPE and LOPE and acknowledging the role of the immune landscape in the eventual interference and tailored treatment of EOPE.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3676","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T10:46:32Z","timestamp":1708080392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Comparison of immune\u2010related gene signatures and immune infiltration features in early\u2010 and late\u2010onset preeclampsia"],"prefix":"10.1002","volume":"26","author":[{"given":"Quanfeng","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"},{"name":"Xiamen Key Laboratory of Basic and Clinical Research on Major Obstetrical Diseases Xiamen  Xiamen China"},{"name":"Xiamen Clinical Research Center for Perinatal Medicine  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics Shanghai Jiaotong University School of Medicine Xinhua Hospital  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanxi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueyan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"},{"name":"Xiamen Key Laboratory of Basic and Clinical Research on Major Obstetrical Diseases Xiamen  Xiamen China"},{"name":"Xiamen Clinical Research Center for Perinatal Medicine  Xiamen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Women and Children's Hospital, School of Medicine Xiamen University  Xiamen China"},{"name":"Xiamen Key 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