Assessing the role of IL-35 in colorectal cancer progression and prognosis

Int J Clin Exp Pathol. 2013 Aug 15;6(9):1806-16. eCollection 2013.

Abstract

Despite the recent realization of Interleukin (IL)-35 in tumorigenesis, its exact impact on colorectal cancer (CRC) progression and prognosis, however, is yet to be elucidated clearly. We thus in the present report conducted comparative analysis of IL-35 levels between CRC patients and matched control subjects. IL-35 is highly expressed in all CRC tissues, which can be detected in vast majority of colorectal cancer cells. IL-35 levels in CRC lysates and serum samples are highly correlated to the severity of malignancy and the clinical stage of tumor. Particularly, a significant reduction for serum IL-35 was noted in patients after surgical resection, indicating that IL-35 promotes CRC progression associated with poor prognosis. Mechanistic study demonstrated a significant correlation between serum IL-35 levels and the number of peripheral regulatory T (Treg) cells in CRC patients, suggesting that IL-35 implicates in CRC pathogenesis probably by inducing Treg cells, while cancer cell-derived IL-35 may also recruit Treg cells into the tumor microenvironment in favor of tumor growth. Together, our data support that IL-35 could be a valuable biomarker for assessing CRC progression and prognosis in clinical settings.

Keywords: EBI3; IL-12p35; Interleukin-35; colorectal cancer; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins / metabolism
  • Chemotaxis, Leukocyte
  • Colectomy
  • Colorectal Neoplasms / blood
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / surgery
  • Disease Progression
  • Female
  • Humans
  • Interleukins / blood
  • Interleukins / metabolism*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Neoplasm Grading
  • Neoplasm Staging
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Treatment Outcome
  • Tumor Microenvironment
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • CDCA5 protein, human
  • Cell Cycle Proteins
  • EBI3 protein, human
  • Interleukins
  • Minor Histocompatibility Antigens
  • interleukin-35, human