Increased HSF1 expression predicts shorter disease-specific survival of prostate cancer patients following radical prostatectomy

Johanna K Björk, Ilmari Ahonen, Tuomas Mirtti, Andrew Erickson, Antti Rannikko, Anna Bützow, Stig Nordling, Johan Lundin, Mikael Lundin, Lea Sistonen, Matthias Nees, Malin Åkerfelt

Research output: Contribution to journalArticleScientificpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)31200-31213
Number of pages14
JournalOncotarget
Volume9
Issue number58
DOIs
Publication statusPublished - 27 Jul 2018
MoE publication typeA1 Journal article-refereed

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