Profile and clinical significance of interferon gamma-inducible protein-10 (IP-10) and its receptor in patients with hepatocellular carcinoma

J Cancer Res Clin Oncol. 2023 Nov;149(16):14879-14888. doi: 10.1007/s00432-023-05265-1. Epub 2023 Aug 20.

Abstract

Background: Chemokines play a vital role in tumor progression, metastasis and prognosis; however, the profile and clinical significance of gamma interferon-inducible protein-10 (IP-10) and its receptor (CXCR3) in patients with hepatocellular carcinoma (HCC) have not been well evaluated.

Methods: Liquid-phase chip technology was used to detect the serum IP-10 in 85 patients with HBV-related HCC, 50 patients with chronic hepatitis B (CHB) and 50 liver cirrhosis subjects (CS); simultaneously, the CXCR3 and Alpha fetoprotein (AFP) were determined. Additionally, their mRNA or protein expression levels in peripheral blood mononuclear cells (PBMC), liver tumor and paracancerous tissues were quantified using qRT-PCR or ELISA. Moreover, the IP-10 and CXCR3 expression was verified by the online data from Gene Expression Omnibus. Furthermore, the relationships of serum IP-10, CXCR3 and AFP levels with their overall survival rate were also analyzed.

Results: The levels of IP-10 and CXCR3 in HCC group were significantly higher than those in CHB and CS groups, and their mRNA of PBMC is significantly positive correlation with those in their liver tissues or HBV DNA load (P < 0.0001), respectively. The serum IP-10 and CXCR3 in HCC were significantly correlated with tumor differentiation, metastases staging and distant metastasis (P < 0.05), but not related to gender, age and tumor size (P > 0.05, except IP-10 based on age).

Conclusions: The serum IP-10 (142.6 pg/mL) and CXCR3 (241.2 pg/mL) could be differential diagnostic surrogates that distinguish HCC from CS, and the lower IP-10 level may be conducive to the postoperative survival of HCC patients. Moreover, the IP-10 and CXCR3 would be related to anti-tumor immunity in HCC patients and be a potential target for treatment of HCC.

Keywords: CXCR3; Diagnostics; HCC; IP-10; Pathogenesis.

MeSH terms

  • Carcinoma, Hepatocellular* / metabolism
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Clinical Relevance
  • Humans
  • Interferon-gamma
  • Leukocytes, Mononuclear / metabolism
  • Liver Cirrhosis / pathology
  • Liver Neoplasms* / metabolism
  • RNA, Messenger
  • alpha-Fetoproteins / metabolism

Substances

  • alpha-Fetoproteins
  • Chemokine CXCL10
  • Interferon-gamma
  • RNA, Messenger
  • CXCL10 protein, human