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

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.

High Serum Levels of the Interleukin-33 Receptor Soluble ST2 as a Negative Prognostic Factor in Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, usually arises in the setting of liver cirrhosis (LC), and has a poor prognosis. The recently discovered Th2-cytokine interleukin-33 (IL-33) is a possible mediator in pancreatic and gastric carcinogeneses. IL-33 binds to its receptor and to soluble ST2 (sST2), which thereby acts as a regulator. The role of IL-33 and sST2 in HCC has not been elucidated yet. METHODS: We conducted a case-control study with 130 patients and 50 healthy controls (HCs). Sixty-five patients suffered from HCC and 65 patients had LC without HCC. We assessed serum IL-33 and sST2 levels and their association with established prognostic scores, liver function parameters, and overall survival (OS). RESULTS: No significant difference in IL-33 serum levels was found in HCC compared to LC and HCs. IL-33 levels did not correlate with OS, liver function parameters, the Model for End-Stage Liver Disease (MELD) score, or the Cancer of the Liver Italian Program (CLIP) score. sST2 levels were significantly elevated in LC and HCC patients compared to HCs (P < .0001). Mean sST2 levels in LC were higher than in HCC (P < .0001), but a significant association with OS was only observed in the HCC group (P = .003). sST2 in HCC correlated with the CLIP score, the MELD score, and liver function parameters. CONCLUSION: In the present study, the serum concentration of sST2 was associated with OS of HCC. Therefore, sST2 may be considered as a new prognostic marker in HCC and is worth further evaluation.