Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC)
Arévalo, Jazmine (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Lorente, David (Hospital Universitari Vall d'Hebron)
Trilla Herrera, Enrique (Hospital Universitari Vall d'Hebron)
Salcedo, Maria-Teresa (Hospital Universitari Vall d'Hebron)
Morote Robles, Juan (Hospital Universitari Vall d'Hebron)
Meseguer Navarro, Anna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data:	2021
Resum:	Clear cell renal cell carcinoma (ccRCC) is the most frequent and aggressive subtype of renal carcinoma. So far, the basis of its oncogenesis remains unclear resulting in a deficiency of usable and reliable biomarkers for its clinical management. Previously, we showed that nuclear expression of the signal transducer and activator of transcription 3 (STAT3), phosphorylated at its serine 727 (pS727), was inversely proportional to the overall survival of ccRCC patients. Therefore, in the present study, we validated the value of pS727-STAT3 as a clinically relevant biomarker in ccRCC. This work is a retrospective study on 82 ccRCC patients treated with nephrectomy and followed-up for 10 years. Immunohistochemical expression of pS727-STAT3 was analyzed on a tissue microarray and nuclear and cytosolic levels were correlated with clinical outcome of patients. Our results showed that pS727-STAT3 levels, whether in the nucleus (p = 0. 002; 95% CI 1. 004-1. 026) or the cytosol (p = 0. 040; 95% CI 1. 003-1. 042), significantly correlate with patients' survival in an independent-manner of clinicopathological features (Fuhrman grade, risk group, and tumor size). Moreover, we report that patients with high pS727-STAT3 levels who undergone adjuvant therapy exhibited a significant stabilization of the disease (~ 20 months), indicating that pS727-STAT3 can pinpoint a subset of patients susceptible to respond well to treatment. In summary, we demonstrated that high pS727-STAT3 levels (regardless of their cellular location) correlate with low overall survival of ccRCC patients, and we suggested the use of pS727-STAT3 as a prognostic biomarker to select patients for adjuvant treatment to increase their survival.
Ajuts:	Ministerio de Economía y Competitividad SAF201459945-R Ministerio de Economía y Competitividad 12/0021/0013
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Tumour biomarkers ; Urological cancer
Publicat a:	Scientific reports, Vol. 11 (march 2021) , ISSN 2045-2322

DOI: 10.1038/s41598-021-86218-x
PMID: 33772065

9 p, 2.1 MB

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