HKDC1 in Gastric Cancer: A New Diagnostic, Prognostic Biomarker, and Novel Therapeutic Target

Ann Clin Lab Sci. 2023 Sep;53(5):726-737.

Abstract

Objective: Gastric cancer (GC) has become a significant contributor globally to cancer-related mortalities. Accordingly, there is a critical need to identify a new therapeutic target for GC. Recently, the hexokinase domain containing 1 (HKDC1), an oncogenic factor, has been recognized in various cancers. Nevertheless, the role of HKDC1 in GC still needs to be explored. This study is aimed to investigate the role of HKDC1 in GC.

Methods: Initially, the HKDC1 expression in GC tissue samples and cell lines was analyzed using RT-qPCR, exploring its correlation with overall patient survival. Further, short hairpin RNA (shRNA) technology was employed to establish HKDC1 knockdown in GC cell lines and assess the impact of HKDC1 deficiency on tumor growth in vitro and in vivo.

Results: RT-qPCR results revealed overexpression of HKDC1 in GC tissue samples and cell lines, which could be correlated to shorter patient survival. HKDC1 knockdown led to decreased viability and colony formation ability of GC cells. Moreover, the transwell assay demonstrated that downregulating HKDC1 significantly suppressed the migration and invasion abilities of GC cells. Eventually, the xenograft tumor model derived from HKDC1 knockdown GC cells in mice exhibited reduced tumor size and deprived Ki67 expression, indicating inhibited tumor growth.

Conclusion: The study provided evidence of HKDC1 dysregulation in GC tissues, suggesting its potential as a promising novel target for GC treatment.

Keywords: Biomarker; Gastric cancer; HKDC1; Prognostic factor; targeted therapy.

MeSH terms

  • Animals
  • Biomarkers
  • Cell Line
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Hexokinase / genetics
  • Hexokinase / metabolism
  • Humans
  • Mice
  • Prognosis
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism

Substances

  • Biomarkers
  • Hexokinase
  • HKDC1 protein, human