{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:08:39Z","timestamp":1792613319589,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Oncol.","Current Oncology"],"abstract":"<jats:p>Background: Immune checkpoint inhibitors have improved outcomes in metastatic clear-cell renal cell carcinoma (mRCC), yet clinically applicable tissue biomarkers remain limited. Growth differentiation factor-15 (GDF-15) promotes tumour immune evasion and has emerged as a potential therapeutic target in immuno-oncology. We evaluated the prognostic significance of tumour GDF-15 expression in patients with intermediate-risk clear-cell mRCC treated with second-line nivolumab. Methods: Forty-six patients with intermediate-risk clear-cell mRCC who received nivolumab after one line of tyrosine kinase inhibitor therapy were retrospectively evaluated. Tumour GDF-15 expression was assessed by immunohistochemistry and classified as low (0\u20131+) or high (2\u20133+). Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the development of cancer-associated cachexia were compared between expression groups. Results: High tumour GDF-15 expression was observed in 23 patients (50%). ORR was significantly higher in the low-expression group than in the high-expression group (57% vs. 26%, p = 0.036). Low tumour GDF-15 expression was associated with significantly longer PFS (24.5 vs. 7.5 months; HR 0.38, 95% CI 0.18\u20130.80; p = 0.009) and OS (28.6 vs. 12.6 months; HR 0.43, 95% CI 0.19\u20130.98; p = 0.041). The association with OS remained significant after adjustment for age. The frequency of cancer-associated cachexia did not differ according to tumour GDF-15 expression (43% vs. 35%, p = 0.546). Conclusions: Low tumour GDF-15 expression was associated with better objective response and longer progression-free and overall survival in patients with intermediate-risk metastatic clear-cell renal cell carcinoma treated with second-line nivolumab, with the association with overall survival remaining significant after adjustment for age. Tumour GDF-15 represents a promising tissue biomarker for prognostic risk stratification and warrants validation in larger prospective studies.<\/jats:p>","DOI":"10.3390\/curroncol33090531","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Tumour GDF-15 Expression and Clinical Outcomes in Intermediate-Risk Metastatic Clear-Cell Renal Cell Carcinoma Treated with Second-Line Nivolumab"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0212-1191","authenticated-orcid":false,"given":"Orhun","family":"Akdogan","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betul","family":"Ogut","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osman","family":"Sutcuoglu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melike","family":"Urganci","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burcu Ulas","family":"Kahya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ipek","family":"Isik Gonul","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3492-8818","authenticated-orcid":false,"given":"Hatice Azra Begum","family":"Salimoglu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba","family":"Ugur Tuzcu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ozan","family":"Yazici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Ozet","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuriye","family":"Ozdemir","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Gazi University, 06560 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/annonc\/mdz056","article-title":"Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"30","author":"Escudier","year":"2019","journal-title":"Ann. 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