Abstract

Prostate cancer (PCa) is a slow-growing tumor representing one of the major causes of all new cancer cases and cancer mortality in men worldwide. Although screening methods for PCa have substantially improved, the outcome for patients with advanced PCa remains poor. The elucidation of the molecular mechanism that drives the progression from a slow-growing, organ-confined tumor to a highly invasive and castration-resistant PCa (CRPC) is therefore important. We have already proved the diagnostic potential of indoleamine-2,3-dioxygenase (IDO) when detected in urine of individuals at risk of developing PCa. The aim of this study was to implement IDO as a prognostic marker for PCa patients undergoing surgical treatment. We have thus conducted an observational study by collecting 100 urine samples from patients undergoing radical prostatectomy as first treatment of choice. To test the integrity of our investigation, scale dilution cells of an established PC3 cell line were added to urine of healthy donors and used for gene expression analysis by a TaqMan assay on the catalytic part of IDO mRNA. Our data show that the quantification of IDO mRNA in urine of patients has a very promising ability to identify patients at high risk of cancer advancement, as defined by Gleason score. Our goal is to lay the groundwork to develop a superior test for PCa. The data generated are thus necessary (i) to strengthen the IDO-based diagnostic/prognostic test and (ii) to provide patients and clinicians with an affordable and easy screening test.

Highlights

  • Prostate cancer (PCa) represents the first leading cause of cancer morbidity and the third of cancer death in men in developed countries, with a worldwide incidence rate accounting for 14% of total newly diagnosed cases and a worldwide total cancer mortality rate of 6% [1]

  • Tumor immune escape occurs through the secretion of different tumor-derived factors (TDFs) with immunosuppressive properties, such as indoleamine-2,3dioxygenase (IDO)

  • The specific IDO gene product plays a key role in tryptophan metabolism, and its enhanced activities might result in both the depletion of an amino acid essential for lymphocyte metabolism and in the generation of toxic metabolites [8]

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Summary

Introduction

Prostate cancer (PCa) represents the first leading cause of cancer morbidity and the third of cancer death in men in developed countries, with a worldwide incidence rate accounting for 14% of total newly diagnosed cases and a worldwide total cancer mortality rate of 6% [1]. It is of relevance that prostate tissues appear to be characterized by features consistent with an Prognostic Value of IDO Gene Expression immunosuppressive microenvironment. Infiltrating CD4+ and CD8+ T lymphocytes (TILs) are predominantly characterized by regulatory [2, 3] and functionally exhausted (PD-1+, B7-H1+) phenotypes [4,5,6]. Enhanced suppressive function of adaptive CD4+ Treg has been observed in the peripheral blood of patients with PCa and found to correlate with metastatic behavior [7]. The specific IDO gene product plays a key role in tryptophan metabolism, and its enhanced activities might result in both the depletion of an amino acid essential for lymphocyte metabolism and in the generation of toxic metabolites [8]

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