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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.
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.
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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