title: Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer.
abstract: BACKGROUND
  Chronic 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.
  
  
  METHODS
  Eighty 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 χ(2) 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.
  
  
  RESULTS
  IL-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.
  
  
  CONCLUSIONS
  Expression 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.
authors.affiliation: ICFS, Department of Surgery, Basel University Hospital, Basel, Switzerland. cmengus@uhbs.ch
authors.forename: Chantal
authors.initials: C
authors.lastname: Mengus
authors.forename: Clémentine
authors.initials: C
authors.lastname: Le Magnen
authors.forename: Emanuele
authors.initials: E
authors.lastname: Trella
authors.forename: Kawa
authors.initials: K
authors.lastname: Yousef
authors.forename: Lukas
authors.initials: L
authors.lastname: Bubendorf
authors.forename: Maurizio
authors.initials: M
authors.lastname: Provenzano
authors.forename: Alexander
authors.initials: A
authors.lastname: Bachmann
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli
authors.forename: Stephen
authors.initials: S
authors.lastname: Wyler
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019409:Interleukin-15 / Q000097:blood* / Q000235:genetics; D015851:Interleukin-7 / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D012995:Solubility
chemical_list: D000209:Acute-Phase Proteins; C569274:IL15 protein, human; C508605:IL7 protein, human; D019409:Interleukin-15; D015851:Interleukin-7