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

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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.

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Data availability statement

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

AFP:

Alpha fetoprotein

CHB:

Chronic hepatitis B

ELISA:

Enzyme-linked immunosorbent serologic assay

GEO:

Gene expression omnibus

HCC:

Hepatocellular carcinoma

CS:

Cirrhosis subject

IP-10 (CXCL10):

Gamma interferon-inducible protein-10

CXCR3:

CXC subfamily receptor-3

PBMC:

Peripheral blood mononuclear cells

TNM:

Tumor, nodes, metastases

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Funding

This work was supported by the National Key Research and Development Program of China (2021YFC2301804), the Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project (2023ZL482), and the National Natural Science Foundation of China (Grant no. 82072357).

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Authors and Affiliations

Authors

Contributions

JZ conceived and designed the study. YT and CF performed the experiment and writing the paper. XY and LL contributed to the experiment. XF performed data acquisition and analysis. All authors have carefully read and approved the submitting manuscript.

Corresponding authors

Correspondence to Xuefen Li or Jiezuan Yang.

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The authors declare no competing interests.

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All experiments were performed in accordance with relevant guidelines and regulation.

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Li, Y., Wang, C., Yin, X. et al. 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 149, 14879–14888 (2023). https://doi.org/10.1007/s00432-023-05265-1

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