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Fibroblast Activation Protein Alpha (FAP) Expression Is Associated with Disease Recurrence and Poor Response to Tyrosine Kinase Inhibitors in Advanced Clear Cell Renal Cell Carcinoma

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Vydáno v:International Journal of Molecular Sciences vol. 26, no. 22 (2025), p. 11112-11127
Hlavní autor: Riaza Montes María
Další autoři: Suárez Beatriz, Solano-Iturri Jon Danel, Lecumberri, David, Iturregui, Ane Miren, Lawrie, Charles H, Armesto María, Nunes-Xavier, Caroline E, Pulido, Rafael, López, José I, Angulo, Javier C, Larrinaga Gorka
Vydáno:
MDPI AG
Témata:
Patients
Biomarkers
Kidney cancer
Medical prognosis
Metastasis
Fibroblasts
Tumors
Kinases
Lymphatic system
Proteins
Classification
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Abstrakt:Despite advances in the management of advanced clear cell renal cell carcinoma (ccRCC), robust biomarkers for prognosis and therapeutic response prediction remain elusive. Fibroblast activation protein-α (FAP), a marker of activated cancer-associated fibroblasts (CAFs), has emerged as a potential indicator of tumor aggressiveness and resistance to systemic therapies in various solid tumors. This study evaluated the clinical relevance of stromal FAP expression in a cohort of 137 patients with advanced ccRCC and long-term follow-up. FAP immunohistochemistry (IHC) was performed on primary tumor specimens and correlated with key clinicopathological features, disease-free survival (DFS), overall survival (OS), and radiological response to first-line tyrosine kinase inhibitors (TKIs). A significantly higher percentage of FAP-positive CAFs was observed in primary tumors with high histological grade, extensive local invasion (pT3–4), and advanced clinical stage (NCCN stage III–IV). Stromal FAP expression was associated with shorter DFS and OS. Moreover, tumors lacking FAP expression were more likely to achieve complete response to TKI therapy as defined by RECIST criteria. These findings highlight the potential of FAP IHC as a prognostic and predictive tool in advanced ccRCC and support further clinical validation.
ISSN:1661-6596
1422-0067
DOI:10.3390/ijms262211112
Zdroj:Health & Medical Collection