ZPR1 is an immunodiagnostic biomarker and promotes tumor progression in esophageal squamous cell carcinoma

Cancer Sci. 2024 Jan;115(1):70-82. doi: 10.1111/cas.16004. Epub 2023 Nov 14.

Abstract

To evaluate the potential of zinc finger protein 1 (ZPR1) as a diagnostic biomarker and explore the underlying role for esophageal squamous cell carcinoma (ESCC). A human proteome microarray was customized to identify anti-ZPR1 autoantibody, and enzyme-linked immunosorbent assay (ELISA) was adopted to assess the diagnostic performance of anti-ZPR1 autoantibody in 294 patients with ESCC and 294 normal controls. The expression of ZPR1 protein was measured by immunohistochemistry. The effect of ZPR1 on the proliferation, migration, and invasion of ESCC cells was investigated through CCK-8, wound healing, and Transwell assays. The expression level of anti-ZPR1 autoantibody (fold change = 2.77) in ESCC patients was higher than that in normal controls. The receiver operating characteristic (ROC) analysis manifested anti-ZPR1 autoantibody achieved area under the ROC curve (AUC) of 0.726 and 0.734 to distinguish ESCC from normal controls with sensitivity of 50.0% and 42.3%, and specificity of 91.0% and 92.0% in the test group and validation group, respectively. The positive rate of ZPR1 protein was significantly higher in ESCC tissues (75.5%, 80/106) than paracancerous tissues (9.4%, 5/53). Compared with the human normal esophageal cell line, the expression level of ZPR1 mRNA and protein in ESCC lines (KYSE150, Eca109, and TE1) had an increased trend. The knockdown or overexpression of ZPR1 reduced and enhanced the proliferation, migration, and invasion of ESCC cell, respectively. ZPR1 was a potential immunodiagnostic biomarker for noninvasive detection and could be a promotional factor in tumor progression of ESCC.

Keywords: ZPR1; autoantibody; biomarker; esophageal squamous cell carcinoma; tumor progression.

MeSH terms

  • Autoantibodies / metabolism
  • Biomarkers
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Esophageal Neoplasms* / genetics
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans

Substances

  • Biomarkers
  • Autoantibodies