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

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

doi:10.18632/oncotarget.25756

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.

Highlights

Prostate cancer is one of the most commonly diagnosed male cancer in Western countries, and worldwide approximately one million new prostate cancer cases are diagnosed each year [1]
The results suggest that nuclear Heat shock transcription factor 1 (HSF1) expression could serve as a novel prognostic marker for patient riskstratification on disease progression and survival after radical prostatectomy
Since HSF1 has been demonstrated to be a strong promoter of oncogenesis, we hypothesized that HSF1 would hold clinical significance in prostate cancer

Summary

Introduction

Prostate cancer is one of the most commonly diagnosed male cancer in Western countries, and worldwide approximately one million new prostate cancer cases are diagnosed each year [1]. The clinical course is highly variable; primary prostate cancer often remains indolent, a considerable proportion progresses into castration-resistant prostate cancer. The most widely used tool to evaluate prognosis after primary treatment is Gleason grading, which is based on the glandular pattern of the tumor. Accurate risk-stratification throughout the whole range of patients remains difficult, for intermediate Gleason score tumors that often represent the vast majority of patients [2,3,4]. Tumors with similar histological patterns can exhibit different clinical outcomes [5, 6]. Gleason grading was recently updated to a grade group system [7], and is being used in combination with other established parameters, foremost tumor stage and prostate-specific antigen (PSA), current prognostication is insufficient and accurate riskstratification remains difficult. Novel biomarkers for reliably assessing individual patient’s risk of disease progression and outcome are highly needed

Methods

Results

Conclusion