Immune-related RELT drives clear cell renal cell carcinoma progression through JAK/STAT signaling pathway activation

Yini Wang1,2, Yingying Yang2, Tianqi Wang2

  • 1Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.

Frontiers in Immunology
|December 11, 2025
PubMed
Abstract

Insights

Tumor Necrosis Factor Receptor Superfamily Member 19L (RELT) is highly expressed in clear cell renal cell carcinoma (ccRCC), promoting its development and poor prognosis. RELT influences the tumor immune microenvironment and may serve as a novel biomarker for ccRCC.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) is a significant cause of cancer-related mortality.
  • The role of Tumor Necrosis Factor Receptor Superfamily Member 19L (RELT) in ccRCC pathogenesis and its impact on the tumor immune microenvironment remain incompletely understood.

Purpose of the Study:

  • To investigate the functional role of RELT in ccRCC.
  • To explore the association between RELT expression and clinical prognosis in ccRCC patients.
  • To elucidate the mechanisms underlying RELT's function and its influence on the ccRCC tumor immune microenvironment.

Main Methods:

  • Utilized Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases for differential expression analysis.
  • Performed ex vivo and in vivo experiments to validate RELT function in ccRCC.
  • Conducted pathway analyses (GO, KEGG, GSEA) and immune infiltration analyses (xCELL, EPIC, CIBERSORT, TIMER, TIDE).

Main Results:

  • RELT is significantly upregulated in ccRCC tissues and correlates with poor prognosis.
  • Functional assays demonstrated that RELT promotes malignant biological behaviors in ccRCC cells.
  • RELT influences humoral immunity, cellular chemotaxis, cytokine regulation, and is associated with immune cells like B cells, CD8+ T cells, CD4+ T cells, and macrophages, impacting the tumor immune microenvironment.

Conclusions:

  • RELT promotes ccRCC development and progression.
  • RELT plays a crucial role in modulating the ccRCC tumor immune microenvironment, thereby affecting patient prognosis.
  • RELT represents a potential novel biomarker for immune infiltration and prognosis in ccRCC.

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