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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Publicado en:International Journal of Molecular Sciences vol. 26, no. 22 (2025), p. 11112-11127
Autor principal: Riaza Montes María
Otros Autores: 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
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024 7 |a 10.3390/ijms262211112  |2 doi 
035 |a 3275535106 
045 2 |b d20251115  |b d20251130 
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100 1 |a Riaza Montes María  |u Department of Urology, Galdakao-Usansolo University Hospital, 48960 Usansolo, Spain; maria.riazamontes@osakidetza.eus 
245 1 |a 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 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a 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. 
653 |a Patients 
653 |a Biomarkers 
653 |a Kidney cancer 
653 |a Medical prognosis 
653 |a Metastasis 
653 |a Fibroblasts 
653 |a Tumors 
653 |a Kinases 
653 |a Lymphatic system 
653 |a Proteins 
653 |a Classification 
700 1 |a Suárez Beatriz  |u Department of Nursing, Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; beatriz.suarez@ehu.eus 
700 1 |a Solano-Iturri Jon Danel  |u Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; jondanel.solanoiturri@osakidetza.eus (J.D.S.-I.); carolineelisabeth.nunes-xavier@bio-bizkaia.eus (C.E.N.-X.); rpulidomurillo@gmail.com (R.P.); jilpath@gmail.com (J.I.L.) 
700 1 |a Lecumberri, David  |u Department of Urology, Cruces University Hospital, 48903 Barakaldo, Spain; david.lecumberricastanos@osakidetza.eus (D.L.); anemiren.iturreguidelpozo@osakidetza.eus (A.M.I.) 
700 1 |a Iturregui, Ane Miren  |u Department of Urology, Cruces University Hospital, 48903 Barakaldo, Spain; david.lecumberricastanos@osakidetza.eus (D.L.); anemiren.iturreguidelpozo@osakidetza.eus (A.M.I.) 
700 1 |a Lawrie, Charles H  |u Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; charles.lawrie@bio-gipuzkoa.eus (C.H.L.); maria.armestoalvarez@bio-gipuzkoa.eus (M.A.) 
700 1 |a Armesto María  |u Molecular Oncology Group, Biogipuzkoa Health Research Institute, 20014 San Sebastián, Spain; charles.lawrie@bio-gipuzkoa.eus (C.H.L.); maria.armestoalvarez@bio-gipuzkoa.eus (M.A.) 
700 1 |a Nunes-Xavier, Caroline E  |u Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; jondanel.solanoiturri@osakidetza.eus (J.D.S.-I.); carolineelisabeth.nunes-xavier@bio-bizkaia.eus (C.E.N.-X.); rpulidomurillo@gmail.com (R.P.); jilpath@gmail.com (J.I.L.) 
700 1 |a Pulido, Rafael  |u Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; jondanel.solanoiturri@osakidetza.eus (J.D.S.-I.); carolineelisabeth.nunes-xavier@bio-bizkaia.eus (C.E.N.-X.); rpulidomurillo@gmail.com (R.P.); jilpath@gmail.com (J.I.L.) 
700 1 |a López, José I  |u Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; jondanel.solanoiturri@osakidetza.eus (J.D.S.-I.); carolineelisabeth.nunes-xavier@bio-bizkaia.eus (C.E.N.-X.); rpulidomurillo@gmail.com (R.P.); jilpath@gmail.com (J.I.L.) 
700 1 |a Angulo, Javier C  |u <label>11</label>Department of Urology, Hospital Universitario de Getafe, 28907 Getafe, Spain; javier.angulo@salud.madrid.org 
700 1 |a Larrinaga Gorka  |u Biobizkaia Health Research Institute, 48903 Barakaldo, Spain; jondanel.solanoiturri@osakidetza.eus (J.D.S.-I.); carolineelisabeth.nunes-xavier@bio-bizkaia.eus (C.E.N.-X.); rpulidomurillo@gmail.com (R.P.); jilpath@gmail.com (J.I.L.) 
773 0 |t International Journal of Molecular Sciences  |g vol. 26, no. 22 (2025), p. 11112-11127 
786 0 |d ProQuest  |t Health & Medical Collection 
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