Nuclear and cytosolic pS727-STAT3 levels correlate with overall survival of patients affected by clear cell renal cell carcinoma (ccRCC).
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Renal Cell
/ mortality
Female
Humans
Kidney Neoplasms
/ mortality
Male
Middle Aged
Nephrectomy
/ methods
Phosphorylation
Prognosis
Protein Kinase Inhibitors
/ therapeutic use
Retrospective Studies
STAT3 Transcription Factor
/ metabolism
Tissue Array Analysis
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
26 03 2021
26 03 2021
Historique:
received:
23
11
2020
accepted:
08
03
2021
entrez:
27
3
2021
pubmed:
28
3
2021
medline:
21
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 33772065
doi: 10.1038/s41598-021-86218-x
pii: 10.1038/s41598-021-86218-x
pmc: PMC7998019
doi:
Substances chimiques
Biomarkers, Tumor
0
Protein Kinase Inhibitors
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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