Increased HSF1 expression predicts shorter disease-specific survival of prostate cancer patients following radical prostatectomy
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Johanna K. Björk1, Ilmari Ahonen2, Tuomas Mirtti3,4,5, Andrew Erickson4,5, Antti Rannikko6, Anna Bützow3, Stig Nordling3, Johan Lundin4, Mikael Lundin4, Lea Sistonen7,8, Matthias Nees1,* and Malin Åkerfelt1,*
1Institute of Biomedicine, University of Turku, Turku, Finland
2Department of Mathematics and Statistics, University of Turku, Turku, Finland
3Department of Pathology, Medicum, University of Helsinki, Helsinki, Finland
4Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
5Department of Pathology, HUSLAB, Helsinki University Hospital, Helsinki, Finland
6Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
7Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland
8Centre for Biotechnology, University of Turku and Åbo Akademi University, Turku, Finland
*These authors contributed equally to this work
Malin Åkerfelt, email: [email protected]
Keywords: biomarker; heat shock factor; predictive marker; prostate cancer; tissue microarray (TMA)
Received: March 09, 2018 Accepted: June 25, 2018 Published: July 27, 2018
Prostate cancer is a highly heterogeneous disease and the clinical outcome is varying. While current prognostic tools are regarded insufficient, there is a critical need for markers that would aid prognostication and patient risk-stratification. Heat shock transcription factor 1 (HSF1) is crucial for cellular homeostasis, but also a driver of oncogenesis. The clinical relevance of HSF1 in prostate cancer is, however, unknown. Here, we identified HSF1 as a potential biomarker in mRNA expression datasets on prostate cancer. Clinical validation was performed on tissue microarrays from independent cohorts: one constructed from radical prostatectomies from 478 patients with long term follow-up, and another comprising of regionally advanced to distant metastatic samples. Associations with clinical variables and disease outcomes were investigated. Increased nuclear HSF1 expression correlated with disease advancement and aggressiveness and was, independently from established clinicopathological variables, predictive of both early initiation of secondary therapy and poor disease-specific survival. In a joint model with the clinical Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score, nuclear HSF1 remained a predictive factor of shortened disease-specific survival. The results suggest that nuclear HSF1 expression could serve as a novel prognostic marker for patient risk-stratification on disease progression and survival after radical prostatectomy.
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