Tumor specific cytokine pattern explored in renal cell carcinoma
6 affiliations
- 1Department of Urology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China
- 2RayBiotech, Inc., Peachtree Corners, GeorgiaUnited States of America
- 3RayBiotech, Inc., Guangzhou, Guangdong, China
- 4Department of Urology, Hui Ya Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Huizhou, Guangdong, China
- 5South China Biochip Research Center, Guangzhou, Guangdong, China
- 6Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
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.
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BibTeX
@article{chen2026tumor,
title = {{Tumor specific cytokine pattern explored in renal cell carcinoma}},
author = {Xu Chen and Zhuangyao Liao and Rochelle Wickramasekara and Ying Luo and Panning Wang and Sihao Wang and Yunru Chen and Hang Zhou and Shuhong Luo and Shaopeng Qiu and Ruo-Pan Huang},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0358533},
url = {https://doi.org/10.1371/journal.pone.0358533},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Tumor specific cytokine pattern explored in renal cell carcinoma
AU - Xu Chen
AU - Zhuangyao Liao
AU - Rochelle Wickramasekara
AU - Ying Luo
AU - Panning Wang
AU - Sihao Wang
AU - Yunru Chen
AU - Hang Zhou
AU - Shuhong Luo
AU - Shaopeng Qiu
AU - Ruo-Pan Huang
PY - 2026
DA - 2026/09/29
JO - PLOS One
DO - 10.1371/journal.pone.0358533
UR - https://doi.org/10.1371/journal.pone.0358533
AB - 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.
SN - 1932-6203
ER -