Molecular and Clinical Relevance of ZBTB38 Expression Levels in Prostate Cancer.

Maud De Dieuleveult,Anne Jouinot,Claire Marchal,Benoit Miotto,Anne Letessier

doi:10.3390/cancers12051106

Abstract

Prostate cancer is one of the most commonly diagnosed cancers in men. A number of genomic and clinical studies have led to a better understanding of prostate cancer biology. Still, the care of patients as well as the prediction of disease aggressiveness, recurrence and outcome remain challenging. Here, we showed that expression of the gene ZBTB38 is associated with poor prognosis in localised prostate cancer and could help discriminate aggressive localised prostate tumours from those who can benefit only from observation. Analysis of different prostate cancer cohorts indicates that low expression levels of ZBTB38 associate with increased levels of chromosomal abnormalities and more aggressive pathological features, including higher rate of biochemical recurrence of the disease. Importantly, gene expression profiling of these tumours, complemented with cellular assays on prostate cancer cell lines, unveiled that tumours with low levels of ZBTB38 expression might be targeted by doxorubicin, a compound generating reactive oxygen species. Our study shows that ZBTB38 is involved in prostate cancer pathogenesis and may represent a useful marker to identify high risk and highly rearranged localised prostate cancer susceptible to doxorubicin.

Highlights

Prostate cancer is the second most common cancer in men and the sixth leading cause of death from cancer in men around the world [1,2,3,4,5]
In the four cohorts reporting gene expression data in metastatic prostate cancer, we observed a significant decrease of ZBTB38 expression levels in metastatic prostate cancer compared to normal/benign prostate tissues, as well as localised prostate cancer (Table 1 and Figure 1a–c)
We investigated the prognostic value of ZBTB38 expression in prostate cancer patients using biochemical recurrence after primary curative treatment as a readout of disease-free survival

Summary

Introduction

Prostate cancer is the second most common cancer in men and the sixth leading cause of death from cancer in men around the world [1,2,3,4,5]. The Gleason score, the levels of prostate-specific antigen (PSA) and clinical stage are the most commonly used parameters to assess the clinical trajectory of prostate cancer [7]. Based on these classifications, patients are stratified as low-, intermediate- and high-risk of developing aggressive prostate cancer and metastasis. More accurate systems need to be implemented to better predict prostate cancers progression and outcome [8,9]. While Gleason 7 prostate cancer represents intermediate risk prostate cancer, it is shown that Gleason

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Conclusion