Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer

Chantal Mengus,Alexander Bachmann,Lukas Bubendorf,Michael Heberer,Clémentine Le Magnen,Stephen Wyler,Emanuele Trella,Maurizio Provenzano,Kawa Yousef,Giulio C Spagnoli

doi:10.1186/1479-5876-9-162

Chantal Mengus, Alexander Bachmann + Show 8 more

Open Access

https://doi.org/10.1186/1479-5876-9-162

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Abstract

BackgroundChronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera.MethodsEighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers.ResultsIL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign disease. Serum titres of C reactive (CRP), high mobility group B1 (HMGB1) and serum amyloid A (SAA) acute phase proteins were similar in both groups of patients.ConclusionsExpression IL-7 and IL-15 genes in prostate tissues and corresponding serum titres are significantly increased in patients with early stage PCA as compared with patients with BPH.

Highlights

Chronic inflammation has been suggested to favour prostate cancer (PCA) development
In order to evaluate the potential role of these IL in early phases of prostate oncogenesis, in this study we have evaluated the expression of specific genes in prostatic tissues from patients bearing either localized pT12c PCA or benign prostatic hyperplasia (BPH) and we have measured the titres of circulating proteins in their sera
In order to gain insights into events occurring in early stages of prostate cancerogenesis, in this study we evaluated IL gene expression and protein production at local and systemic levels, respectively, in localized PCA, as compared with BPH

Summary

Introduction

Chronic inflammation has been suggested to favour prostate cancer (PCA) development. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor g chain (c-g), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). Chronic inflammation has been suggested to play a major role in prostate oncogenesis[2]. Local and systemic immunosuppression have been reported in patients bearing PCA[3,4,5,6]. Cytokines represent key mediators of inflammation and play pivotal roles in the interaction between immune system and cancer. A number of them have been suggested to be associated with advanced stage PCA[7]. IL-4 and, in particular, IL-6 have been shown to exert antiapoptotic effects on PCA cells, whereas proangiogenic effects of IL-8 have been demonstrated [7]

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