Chromatin licensing and DNA replication factor 1 as a potential prognostic and diagnostic biomarker for gastric cancer

Sci Rep. 2024 Dec 28;14(1):31000. doi: 10.1038/s41598-024-81977-9.

Abstract

Accurate and timely genetic material replication is essential for preserving genomic integrity. The replication process begins with chromatin licensing and DNA replication factor 1 (CDT1). It has been demonstrated that dysregulated CDT1 expression causes genomic instability, damages DNA, and may even cause cancer. Although this protein is overexpressed in several malignancies, its significance in gastric cancer is still unknown. This work aims to investigate the biological function and molecular mechanism of CDT1 in gastric cancer. Bioinformatics studies were carried out using TCGA database, Kaplan-Meier and GEPIA online data analysis software. The expression of CDT1 in stomach cancer tissues was determined by immunohistochemistry, and its relationship to clinicopathological features was examined. Using siRNA and cell function experiments, the impact of CDT1 expression on the capacity of gastric cancer cell lines to proliferate, migrate, and invade was investigated. In gastric cancer tissues, CDT1 is overexpressed and is linked to a dismal prognosis. Through the up-regulation of M-cyc, MCM5 (microchromosome maintenance protein 5), CyclinD1, N-cadherin, and the down-regulation of E-cadherin, CDT1 facilitated the proliferation and invasion of gastric cancer cells. The study's findings shed insight on the possible molecular processes behind CDT1's function in promoting the start and progression of gastric cancer and demonstrate the potential predictive and diagnostic use of CDT1 expression in gastric cancer.

Keywords: CDT1; EMT; Gastric cancer; Invasion; Proliferation.

MeSH terms

  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Prognosis
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • CDT1 protein, human
  • Cell Cycle Proteins
  • MCM5 protein, human
  • Cadherins