Thioredoxin 1 (Trx1) is associated with poor prognosis in clear cell renal cell carcinoma (ccRCC): an example for the crucial role of redox signaling in ccRCC.

Autor: Ribback S; Institute of Pathology, University Medicine, Greifswald, Germany., Winter S; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, University of Tübingen, Tübingen, Germany., Klatte T; Department of Urology, Royal Bournemouth Hospital, Bournemouth, UK., Schaeffeler E; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, University of Tübingen, Tübingen, Germany., Gellert M; Institute of Medical Biochemistry and Molecular Biology, University Medicine, Greifswald, Germany., Stühler V; Department of Urology, University of Tübingen, Tübingen, Germany., Scharpf M; Institute of Pathology, University of Tübingen, Tübingen, Germany., Bedke J; Department of Urology, University of Tübingen, Tübingen, Germany., Burchardt M; Department of Urology, University Medicine, Ferdinand-Sauerbruch-Straße, E17475, Greifswald, Germany., Schwab M; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, University of Tübingen, Tübingen, Germany.; Departments of Clinical Pharmacology, Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany., Lillig CH; Institute of Medical Biochemistry and Molecular Biology, University Medicine, Greifswald, Germany., Kroeger N; Institute of Medical Biochemistry and Molecular Biology, University Medicine, Greifswald, Germany. md.nkroeger@gmail.com.; Department of Urology, University Medicine, Ferdinand-Sauerbruch-Straße, E17475, Greifswald, Germany. md.nkroeger@gmail.com.
Jazyk: angličtina
Zdroj: World journal of urology [World J Urol] 2022 Mar; Vol. 40 (3), pp. 739-746. Date of Electronic Publication: 2021 Dec 02.
DOI: 10.1007/s00345-021-03900-5
Abstrakt: Purpose: Thioredoxins are major regulatory proteins of oxidative signaling. Trx1 is the most prominent thioredoxin and, therefore, the current study sought to evaluate the prognostic role of Trx1 in ccRCC.
Methods and Patients: A tissue micro-array (TMA) study was carried out to evaluate the association of Trx1 with clinicopathological features and survival outcome. Data from the Cancer Genome Atlas (TCGA) were evaluated for the association of characteristics in the Trx1 gene with clinicopathological features and survival outcome.
Results: In the TMA, patients with ccRCC that had high Trx1 levels had lower T stages (p < 0.001), less often distant metastases (p = 0.018), lower nuclear grades (p < 0.001), and less often tumor necrosis (p = 0.037) or sarcomatoid features (p = 0.008). Patients with a combined score of  ≥ 10 had better DSS than patients with a low combined score of < 10 (HR 95% CI 0.62 (0.39-0.98)). Interestingly, the survival outcome is compartment specific: ccRCC patients whose tumors had exclusively Trx1 expression in the cytoplasm had the worst survival outcome (HR 3.1; 95% CI 1.2-8.0). Genomic data from the TCGA demonstrated that patients with ccRCCs that had Trx1 losses had more advanced clinicopathological features and worse survival outcome in disease specific (p < 0.001), overall (p = 0.001), and progression free survival (p = 0.001) when compared to patients with ccRCCs without copy number variations (CNV) or gains.
Conclusion: The current study suggests a possible role of Trx1 in the tumor biology of ccRCC and thus, the current study strongly advises in depth investigations of redox signaling pathways in ccRCC.
(© 2021. The Author(s).)
Databáze: MEDLINE
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