ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicImmunoregulation in Urological Disorders: Novel Targets and TherapiesView all 10 articles
Immune-Related RELT Drives Clear Cell Renal Cell Carcinoma Progression Through JAK/STAT Signaling Pathway Activation
Provisionally accepted
- 1Yantai Affiliated Hospital of Binzhou Medical University, Yantai, China
- 2Yantai Yuhuangding Hospital, Yantai, China
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Objective: The experiment aims to verify the function of Tumor Necrosis Factor Receptor Superfamily Member 19L (RELT) in clear cell renal cell carcinoma (ccRCC). Methods: The relationship between differential expression of RELT in ccRCC and clinical prognosis was investigated based on data from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA) databases. Ex vivo and in vivo experiments were applied to validate the function of RELT in ccRCC. The pathways through which RELT exerts its function were explored using analyses such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes Enrichment Analysis (KEGG), and Gene Set Enrichment Analysis (GSEA). In addition, we applied the algorithms xCELL, Estimating the Proportion of Immune and Cancer cells (EPIC), CIBERSORT, Tumor Immune Estimation Resource (TIMER), and Tumor Immune Dysfunction and Exclusion (TIDE) to analyze the effect of RELT on the ccRCC tumor immune microenvironment. Results: RELT is highly expressed in ccRCC tissues and portends poor prognosis. Functional assays indicate that RELT promotes malignant biological behavior in ccRCC cells. Subsequently, enrichment analysis revealed that RELT functions mainly through humoral immunity, cellular chemotaxis, and cytokine regulation and may serve as a molecule for predicting prognosis in ccRCC. Immune infiltration analysis showed that RELT was significantly associated with immune cells such as B Cells, CD8+ T Cells, CD4+ T Cells, and Macrophages and may affect the tumor immune microenvironment of ccRCC by influencing macrophages. Conclusion: RELT promotes the development of ccRCC and may play a role in regulating the tumor immune microenvironment, which affects the prognosis of ccRCC patients, and RELT may become a new biomarker associated with immune infiltration in ccRCC. Keywords: ccRCC; RELT ; Tumor immune microenvironment; JAK/STAT pathway; Macrophage
Keywords: ccRCC, RELT, Tumor immune microenvironment, JAK/STAT pathway, macrophage
Received: 03 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Yi, Yang, Wang, Ma 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: Jitao Wu, wjturology@163.com
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