Tumor specific cytokine pattern explored in renal cell carcinoma.

Authors

Xu Chen, Zhuangyao Liao, Rochelle Wickramasekara, Ying Luo, Panning Wang, Sihao Wang, Yunru Chen, Hang Zhou, Shuhong Luo, Shaopeng Qiu, Ruo-Pan Huang

Published in

PloS one. Volume 21. Issue 9. Pages e0358533. Epub Sep 29, 2026.

Abstract

Renal cell carcinoma (RCC) is a common urological malignancy, yet the cytokine landscape of the tumor microenvironment, especially in early-stage tumors, remains poorly defined. Using antibody arrays, 174 tumor-related cytokines were measured in 20 sets of normal, para-cancerous, and tumor tissues from early-stage RCC patients. Selected cytokines were validated by ELISA. Functional enrichment was analyzed via DAVID, while transcriptional expression, survival outcomes, and immune infiltration were assessed using GEPIA, Kaplan-Meier Plotter, and TIMER databases. Thirty-four differentially expressed cytokines were identified in tumors versus controls, enriched in cytokine signaling, TNF, PI3K-Akt, Ras, HIF-1, and Toll-like receptor pathways. ELISA confirmed reduced IL-2, IL-15, IGFBP-2, HGF, ErbB3, and FLT3LG, and increased CCL4, CXCL9, and Angiopoietin-2 in tumors. Serum levels of HGF, ErbB3, and CCL4 were decreased in RCC patients, while urinary ErbB3 was also reduced. IL-2, IL-15, and CCL4 were upregulated in T1-T2 metastatic tumors. Several cytokines correlated with poor survival, except ErbB3, which associated with improved outcomes. Several cytokine-related genes, including CXCL9 and CCL4, correlated with inferred immune cell infiltration patterns. These findings suggest that early-stage RCC may be associated with a cytokine expression profile characterized by reduced immune-stimulating factors and elevated pro-angiogenic and inflammatory signals. Urinary ErbB3 emerged as a candidate non-invasive biomarker requiring further validation.

PMID:
42809553
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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