Copper transporter gene ATP7A: A predictive biomarker for immunotherapy and targeted therapy in hepatocellular carcinoma

Int Immunopharmacol. 2023 Jan:114:109518. doi: 10.1016/j.intimp.2022.109518. Epub 2022 Dec 8.

Abstract

Background: ATP7A is an important copper transporter that regulates numerous cellular biological processes. However, the role of ATP7A in immunotherapy and targeted therapy, especially for hepatocellular carcinoma (HCC), remains unknown.

Methods: We analyzed ATP7A expression and its effect on digestive system tumor prognoses, assessed its expression in tissue microarrays from 319 HCC patients, and investigated the relationship between ATP7A expression and tumor immunity. Specifically, we evaluated the possible association between ATP7A and programmed death ligand 1 (PD-L1) expression in human HCC tissues. Finally, we analyzed the effect of ATP7A on sorafenib efficacy in HCC.

Results: ATP7A is generally highly expressed in digestive system tumors but related to poor prognosis only in HCC. ATP7A levels are positively associated with immune cell infiltration and immune checkpoint expression (especially PD-L1). HCC patients coexpressing APT7A and PD-L1 demonstrate poor prognoses. Moreover, HCC patients with high ATP7A levels were more sensitive to sorafenib and demonstrated higher survival rates after sorafenib treatment.

Conclusions: This study provides insights into the correlation between ATP7A levels and tumor immune infiltration and immune checkpoint function in HCC, sheds light on the significance of ATP7A in cancer progression, and provides guidance for more effective and general therapeutic strategies.

Keywords: ATP7A; Biomarker; Hepatocellular carcinoma; PD-L1; Prognosis.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Copper Transport Proteins
  • Copper-Transporting ATPases / genetics
  • Copper-Transporting ATPases / metabolism
  • Humans
  • Immunotherapy
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Peptide Fragments / metabolism
  • Sorafenib / therapeutic use

Substances

  • Sorafenib
  • B7-H1 Antigen
  • Copper Transport Proteins
  • Biomarkers, Tumor
  • ATP7A protein, human
  • Copper-Transporting ATPases
  • ATP7A protein, human (2-79)
  • Peptide Fragments