Copy number alterations and epithelial‑mesenchymal transition genes in diffuse and intestinal gastric cancers in Mexican patients

Mol Med Rep. 2022 May;25(5):191. doi: 10.3892/mmr.2022.12707. Epub 2022 Apr 1.

Abstract

Gastric cancer (GC) is a common malignancy with the highest mortality rate among diseases of the digestive system, worldwide. The present study of GC alterations is crucial to the understanding of tumor biology and the establishment of important aspects of cancer prognosis and treatment response. In the present study, DNA from Mexican patients with diffuse GC (DGC), intestinal GC (IGC) or non‑atrophic gastritis (NAG; control) was purified and whole‑genome analysis was performed with high‑density arrays. Shared and unique copy number alterations (CNA) were identified between the different tissues involving key genes and signaling pathways associated with cancer. This led to the molecular distinction and identification of the most relevant molecular functions to be identified. A more detailed bioinformatics analysis of epithelial‑mesenchymal transition (EMT) genes revealed that the altered network associated with chromosomal alterations included 11 genes that were shared between DGC, IGC and NAG, as well as 19 DGC‑ and 7 IGC‑exclusive genes. Furthermore, the main molecular functions included adhesion, angiogenesis, migration, metastasis, morphogenesis, proliferation and survival. The present study provided the first whole‑genome high‑density array analysis in Mexican patients with GC and revealed shared and exclusive CNA‑associated genes in DGC and IGC. In addition, a bioinformatics‑predicted network was generated, focusing on CNA‑altered genes associated with EMT and the hallmarks of cancer, as well as precancerous alterations that may lead to GC. Molecular signatures of diffuse and intestinal GC, predicted bioinformatically, involve common and distinct CNA‑EMT genes related to the hallmarks of cancer that are potential candidates for screening biomarkers of GC, including early stages.

Keywords: CNA; EMT; copy number alterations; epithelial‑mesenchymal transition; gastric cancer; high‑density arrays.

MeSH terms

  • Computational Biology
  • DNA Copy Number Variations
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mexico
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology

Grants and funding

The present study was supported by the Fondo de Investigación en Salud-Instituto Mexicano del Seguro Social (grant nos. FIS/IMSS/PROT/G16/1573 and FIS/IMSS/PROT/PRIO/13/027).