High plasma sST2 levels in gastric cancer and their association with metastatic disease

Cancer Biomark. 2016;16(1):117-25. doi: 10.3233/CBM-150547.


Background: Gastric cancer (GC) is one of the most common and devastating tumor conditions. Its development is closely linked to an infection with Helicobacter pylori and chronic, cytokine-driven inflammation. The proinflammatory cytokine Interleukin-33 (IL-33), its membrane bound cellular receptor ST2L and its soluble receptor sST2 have recently been identified as important factors in various tumor conditions, but their role in GC remains ill-defined.

Methods: Thirty patients with adenocarcinoma of the stomach or the esophagogastric junction were prospectively enrolled in the current study. 51 patients with Helicobacter pylori positive or negative gastritis and 40 healthy volunteers served as control group. Levels of IL-33 and sST2 were determined by ELISA and their relation to HP-status, tumor stage and survival was assessed.

Results: Soluble ST2 levels in GC were significantly higher than in gastritis or healthy controls (p< 0.0001). Furthermore, higher levels of sST2 were seen in patients with lower degree of tumor differentiation. Soluble ST2 was significantly associated with a more advanced tumor stage (p= 0.018), metastatic disease (p= 0.014) and significantly correlated with the duration of the disease (p= 0.0017). Calculating the ratio of IL-33/sST2 allowed the discrimination of tumor and non-tumor patients.

Conclusion: Soluble ST2 is associated with advanced and metastatic disease in GC patients and significantly correlates with the duration of the disease. The IL-33/sST2 ratio may offer a new, interesting approach in identifying GC patients.

Keywords: Gastric cancer; Helicobacter pylori; inflammation; interleukin-33; sST2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Bacterial / immunology
  • Biomarkers
  • Case-Control Studies
  • Cytokines / blood
  • Female
  • Helicobacter pylori / immunology
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33 / blood
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Receptors, Cell Surface / blood*
  • Stomach Neoplasms / blood*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Young Adult


  • Antibodies, Bacterial
  • Biomarkers
  • Cytokines
  • IL1RL1 protein, human
  • Inflammation Mediators
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Receptors, Cell Surface