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. 2025 Feb 25:13:e18928.
doi: 10.7717/peerj.18928. eCollection 2025.

Analysis of biopsies of gastric cancer, intestinal and diffuse, and non-atrophic gastritis: an overview of loss of heterozygosity in Mexican patients

Affiliations

Analysis of biopsies of gastric cancer, intestinal and diffuse, and non-atrophic gastritis: an overview of loss of heterozygosity in Mexican patients

Violeta Larios-Serrato et al. PeerJ. .

Abstract

This study analyzed the loss of heterozygosity (LOH) effect on gastric cancer (GC) tumor samples from 21 Mexican patients, including diffuse (DGC) and intestinal (IGC) subtypes, as well as non-atrophic gastritis (NAG, control). Whole-genome high-density arrays were performed, and LOH regions were identified among the tissue samples. The differences in affected chromosomes were established among groups, with chromosomes 6 and 8 primarily affected in DGC and chromosomes 3, 16, and 17 in IGC. Functional pathway analysis revealed involvement in cancer-associated processes, such as signal transduction, immune response, and cellular metabolism. Five LOH-genes (IRAK1, IKBKG, PAK3, TKTL1, PRPS1) shared between GC and NAG suggest an early role in carcinogenesis. Specific genes were highlighted for Hallmarks of Cancer NAG-related genes (PTPRJ and NDUFS) were linked to cell proliferation and growth; IGC genes (GNAI2, RHOA, MAPKAPK3, MST1R) to genomic instability, metastasis, and arrest of cell death; and DGC genes to energy metabolism and immune evasion. These findings emphasize the role of LOH in GC pathogenesis and underscore the need for further research to understand LOH-affected genes and their diagnostic or evolution potential in cancer management. Portions of this text were previously published as part of a preprint (https://www.medrxiv.org/content/10.1101/2024.07.29.24311063v1).

Keywords: Diffuse gastric cancer; Gene markers; High density arrays; Intestinal gastric cancer; LOH.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Profile of LOH-genes in gastric cancer from ≥ 3 patients.
(A) The Venn diagram presents frequencies of specific and shared genes in diffuse gastric cancer (DGC), intestinal gastric cancer (IGC), or non-atrophic gastritis (NAG) in LOH. Each subset of the Venn diagram in parentheses indicates the Cancer Hallmark genes (B, C, and D). In the radial graphs, each bar represents a Hallmark and the height of the p.adjust value of the category enrichment; the grays have no significance. The red dotted line represents the significance cut-off value (p.adjust < 0.05).
Figure 2
Figure 2. Relevant gene networks, and the Hallmarks of Cancer and metabolic pathways.
Ten Hallmarks are shown in the legend. The IGC-DGC-NAG network is indicated in purple, NAG in pink, and IGC in blue.

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