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Updated: May 23, 2026
07:50
Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Molecular and structural reprogramming of gastric cancer revealed by systems-level transcriptomic analysis
Negar Mottaghi-Dastjerdi1, Mohammad Soltany-Rezaee-Rad2
1Department of Pharmacognosy and Pharmaceutical Biotechnology, School of Pharmacy, Iran University of Medical Sciences, Tehran, Iran.
Plos One
|May 21, 2026
Summary
Gastric cancer (GC) progression involves developmental gene reactivation and loss of normal cell identity. This study reveals epigenetic changes and FGFR signaling driving cancer, offering new diagnostic and therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Gastric cancer (GC) presents significant mortality challenges due to late diagnosis and treatment resistance.
- Existing transcriptomic studies often lack integration with clinicopathological data and tissue pathobiology.
- Understanding GC's molecular heterogeneity is crucial for improved diagnostics and therapeutics.
Purpose of the Study:
- To identify molecular signatures reflecting gastric tissue reprogramming during malignant transformation using an integrative approach.
- To correlate molecular signatures with clinicopathological variables and tissue-level pathobiology.
- To establish a molecular pathology framework for GC progression.
Main Methods:
- Applied an integrative transcriptomic and network-based framework to RNA-seq data and clinical annotations.
- Utilized non-parametric differential expression filtering, functional enrichment, and protein-protein interaction network modeling.
- Evaluated expression patterns across clinicopathological strata (stage, grade, nodal status, metastasis) and via network-informed clustering.
Main Results:
- Identified a consistent signature of developmental gene reactivation (e.g., HOX genes, HIST1H3J) and loss of gastric epithelial identity across clinical strata.
- Observed persistent downregulation of differentiation markers (e.g., ATP4A, KCNE2) and secretory lineage genes, indicating suppressed parietal/ductal programs.
- Highlighted FGFR-centered signaling as a key oncogenic axis linked to proliferation and invasion, with stage-dependent repression of ADIPOQ associated with poorer survival.
Conclusions:
- GC progression is characterized by coordinated chromatin-level developmental reprogramming and loss of differentiation programs.
- FGFR-driven oncogenic signaling and stage-dependent metabolic disruption are integral to GC pathogenesis.
- Identified molecular signatures serve as candidate diagnostic/prognostic biomarkers and highlight therapeutically actionable pathways for GC.
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