Interleukin-22 serum levels are a negative prognostic indicator in patients with hepatocellular carcinoma

Authors

  • Oliver Waidmann M.D.,

    1. Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author
  • Bernd Kronenberger M.D.,

    1. Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author
  • Patrick Scheiermann M.D.,

    1. Pharmazentrum Frankfurt, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    2. Klinik für Anästhesiologie, Klinikum der Ludwig-Maximilian-Universität, München, Germany
    Search for more papers by this author
  • Verena Köberle Ph.D.,

    1. Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author
  • Heiko Mühl Ph.D.,

    1. Pharmazentrum Frankfurt, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author
  • Albrecht Piiper M.D., Ph.D.

    1. Medizinische Klinik 1, Schwerpunkt Gastroenterologie und Hepatologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt/Main, Germany
    Search for more papers by this author

  • Potential conflict of interest: Nothing to report.

To the Editor:

Interleukin (IL)-22 is a member of the IL-10 cytokine family and is secreted by activated T cells, dendritic cells, and several different kinds of natural killer (NK)-like cells.[1] IL-22 activates the transcription factor signal transducer and activator of transcription (STAT)-3 and induces an acute phase reaction. Interestingly, IL-22 acts predominantly on epithelial cells and protects hepatocytes from death.[2] However, overexpression of IL-22 in the liver favors murine carcinogenesis by activation of STAT-3.3 We have recently found an association between disease severity as well as overall survival with IL-22 serum levels in patients with advanced liver cirrhosis.[4] In light of the emerging key role of IL-22 in hepatocellular carcinoma (HCC),[3] we assessed serum IL-22 levels in a cohort of 156 HCC patients (79.5% males) with mainly alcoholic and hepatitis C virus (HCV)-related liver disease. Concurring with other studies originating from Europe,[5, 6] we recently defined a serum IL-22 concentration of 18 pg/mL as the threshold, discriminating normal from elevated systemic levels of this cytokine.[4] In agreement with our previous data, we found herein also in HCC patients that elevated IL-22 levels (>18 pg/mL, R&D Systems, Quantikine) were significantly associated with shorter overall survival (OS) (P = 0.035, hazard ratio [HR] 0.491, 95% confidence interval [CI] 0.254-0.950) (Fig. 1). In multivariate Cox regression analysis with forward stepwise likelihood ratio including the dichotome variables age (≤65 years versus >65 years), gender, BCLC stage (A versus B-D), and IL-22 (≤18 pg/mL versus >18 pg/mL), high serum IL-22 was independently associated from the other factors with a shorter OS.

Figure 1.

Overall survival of patients with low and high IL-22 levels. The OS rates of patients were calculated with a univariate Cox regression model. Patients at risk for the indicated timepoints are shown.

We conclude that high serum IL-22 concentrations indicate a poor prognosis in patients with HCC and may reflect increased aggressiveness of liver cancer disease.

  • Oliver Waidmann, M.D.1

  • Bernd Kronenberger, M.D.1

  • Patrick Scheiermann, M.D.2,3

  • Verena Köberle, Ph.D.1

  • Heiko Mühl, Ph.D.2

  • Albrecht Piiper, M.D., Ph.D.1

  • 1Medizinische Klinik 1

  • Schwerpunkt Gastroenterologie und Hepatologie

  • Klinikum der Goethe-Universität Frankfurt

  • Frankfurt/Main, Germany

  • 2Pharmazentrum Frankfurt

  • Klinikum der Goethe-Universität Frankfurt

  • Frankfurt/Main, Germany

  • 3Klinik für Anästhesiologie

  • Klinikum der Ludwig-Maximilians-Universität

  • München, Germany

Ancillary