The association of serum IL-33/ST2 expression with hepatocellular carcinoma

BMC Cancer. 2023 Jul 28;23(1):704. doi: 10.1186/s12885-023-11179-5.

Abstract

Background: IL-33 is a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially in patients with hepatocellular carcinoma (HCC), remains controversial. Therefore, we conducted a study of 565 patients with HCC and 561 healthy controls and performed a meta-analysis to quantitatively evaluate the above problems.

Methods: We collected blood from 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentrations of IL-33 and ST2 in the serum, and RT‒PCR was used to detect the levels of IL-33 and ST2 mRNA. Meanwhile, we collected comprehensive literature on IL-33 and the clinical characteristics of cancer patients retrieved from the PubMed, Web of Science and CNKI databases as of December 2022. An odds ratio (OR) with a 95% confidence interval (CI) was used to estimate the impact through overall and stratified analyses.

Results: Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased (p < 0.05), while the levels of IL-33 mRNA and serum showed no significant difference between the two groups (p > 0.05). In the meta-analysis section, at the tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis, and tumor size. Compared with patients with low IL-33 expression, the 3-year overall survival (OS) rate (OR = 3.467, p < 0.001) and 5-year OS rate (OR = 2.784, p < 0.001) of patients with high IL-33 expression were lower. At the serum expression level, the overall analysis showed that the expression of IL-33 increased the risk of cancer, and the serum level of IL-33 was positively correlated with tumor stage and vascular invasion.

Conclusion: IL-33/ST2 is a useful predictive or prognostic biomarker in clinical evaluation and may be used as a potential therapeutic target, but much research is needed to verify this hypothesis.

Keywords: Cancer risk; Hepatocellular carcinoma; IL-33; Meta; Prognosis; ST2.

Publication types

  • Meta-Analysis

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein* / genetics
  • Interleukin-33* / genetics
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Prognosis
  • RNA, Messenger / genetics

Substances

  • Biomarkers, Tumor
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • RNA, Messenger
  • IL1RL1 protein, human