{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:00:46Z","timestamp":1790704846753,"version":"4.1.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81572522"],"award-info":[{"award-number":["81572522"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81202011"],"award-info":[{"award-number":["81202011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Innovation Platform Project","award":["2012B090600021"],"award-info":[{"award-number":["2012B090600021"]}]},{"name":"Guangzhou 2024 Annual Special Project on Agricultural and Social Development Science and Technology","award":["2024B03J1332, 2024B03J1249"],"award-info":[{"award-number":["2024B03J1332, 2024B03J1249"]}]},{"name":"National Key R&D Program of China","award":["2024YFA1307601, 2024YFA1307602, 2024YFA1307603"],"award-info":[{"award-number":["2024YFA1307601, 2024YFA1307602, 2024YFA1307603"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1371\/journal.pone.0358533","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:23:28Z","timestamp":1790702608000},"page":"e0358533","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor specific cytokine pattern explored in renal cell carcinoma"],"prefix":"10.1371","volume":"21","author":[{"given":"Xu","family":"Chen","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"],"department":["Department of Urology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuangyao","family":"Liao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, Sun Yat-Sen University","place":["Guangzhou, Guangdong, China"],"department":["Department of 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