ORIGINAL RESEARCH article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 12 - 2025 | doi: 10.3389/fmolb.2025.1600808
NR1H4 and IL4R as diagnostic biomarkers in OCCC
Provisionally accepted
- 1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- 2Qingtongxia People's Hospital, Ningxia Hui Autonomous Region, China
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Objective Ovarian clear cell carcinoma (OCCC) is characterized by poor prognosis and limited early diagnostic markers. Identifying molecular distinctions between OCCC and the more common high-grade serous ovarian cancer (HGSC) is critical to developing targeted diagnostic and therapeutic strategies for improved clinical outcomes.We retrieved the mRNA expression profiles of OCCC and HGSC from the Gene Expression Omnibus (GEO) database. To identify differentially immune-related genes (DIRGs) linked to OCCC. We assessed DIRGs functional enrichment and built a protein-protein interaction (PPI) to explore DIRGs interactions. Least Absolute Shrinkage and Selection Operator (LASSO) regression model and Multiple Support Vector Machine Recursive Feature Elimination (mSVM-RFE) methods were applied to identify predictive genes. The diagnostic performance of these candidate genes was evaluated using receiver operating characteristic (ROC) curves. A nomogram was constructed to predict OCCC. We further validated key DIRGs' diagnostic ability via a validation set and immunohistochemistry (IHC). The CIBERSORT algorithm was used to analyze correlations between DIRGs and immune cell types in OCCC.We detected 10 DIRGs in OCCC compared to HGSC. These genes were mainly linked to collagen-rich extracellular matrix, Phosphoinositide-3 Kinase-Protein Kinase B (PI3K-AKT) pathway, and transcriptional dysregulation in cancer. Nuclear receptor subfamily 1 group H member 4 (NR1H4) and Interleukin-4 Receptor (IL4R) emerged as potential biomarkers for OCCC (AUCNR1H4 =0.809; AUCIL4R =0.840). In the validation cohort, AUCNR1H4=0.848 and AUCIL4R=0.821, respectively. IHC revealed higher expression levels of NR1H4 and IL4R in OCCC (P < 0.05). Additionally, NR1H4 correlated positively with resting memory T cells and neutrophils, while IL4R correlated with resting Natural Killer (NK) cells and neutrophils.Conclusion NR1H4 and IL4R are promising immune-related diagnostic biomarkers for OCCC, with potential roles in neutrophil-mediated tumor microenvironment modulation. These findings enhance understanding of OCCC pathogenesis and provide a foundation for developing targeted diagnostic tools and immunotherapeutic strategies.
Keywords: Bioinformatics analysis, NR1H4, IL4R, Immune infiltration, Ovarian clear cell carcinoma
Received: 26 Mar 2025; Accepted: 03 Jun 2025.
Copyright: © 2025 Ke, Liang, Zhou, Xie, Huang, Sheng, Wang, Zhou and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Zhuna Wu, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
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