RIPK3 mRNA level acts as a diagnostic biomarker in hepatitis B virus-associated hepatocellular carcinoma

Pathol Res Pract. 2020 Oct;216(10):153147. doi: 10.1016/j.prp.2020.153147. Epub 2020 Jul 28.

Abstract

HBV-associated hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide, and non-invasive early detection of HBV-associated HCC requires to be improved. To determine the alteration and clinical relevance of necroptosis and its key regulator receptor-interacting protein kinase 3 (RIPK3) in HBV-associated HCC, we detected the mRNA level of RIPK3 in peripheral blood mononuclear cells (PBMCs) and analyzed its correlation with clinical parameters. Here, we demonstrate that the expression of RIPK3 is elevated in patients with HBV-associated HCC compared to patients with chronic hepatitis B (CHB) and patients with HBV-related liver cirrhosis (LC). The mRNA level of RIPK3 is positively correlated with the severity of clinical manifestations and TNM stages. Moreover, the serum levels of RIPK3-asssocited cytokines are altered in consistent with the change of RIPK3 expression. The diagnostic accuracy of RIPK3 mRNA level is comparable to AFP test in discriminating HBV-associated HCC from LC and is better than AFP test in discriminating HBV-associated HCC from CHB. The combination of RIPK3 mRNA level and AFP test significantly improves the diagnosis of HBV-associated HCC. These data suggest that RIPK3 mRNA level is a biomarker in the onset and progression of HBV-associated HCC and may provide novel diagnostic strategies combined with the AFP test.

Keywords: Diagnosis; Hepatocellular carcinoma; Necroptosis; Peripheral blood mononuclear cells; Receptor-interacting protein kinase 3.

MeSH terms

  • Adult
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Female
  • Hepatitis B virus / genetics*
  • Hepatitis B, Chronic / complications
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Liver Cirrhosis / pathology
  • Liver Cirrhosis / virology*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism*

Substances

  • Biomarkers, Tumor
  • RIPK3 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinases