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Coexpressed modular gene expression reveals inverse correlation between immune responsive transcription and
Kalaivani Kalamohan1, Dhanasekaran Rathinam1, Ponmathi Panneerpandian1
1Unit of Excellence in Cancer Genetics, Department of Genetics, School of Biological Sciences, Centre for Excellence in Genomic Sciences, Madurai Kamaraj University, Madurai, 625021, India.
Abstract:
The existing large number of gene expression profiles of tumour samples offers a great advantage for the integrative functional genomic exploration of molecular dysregulation in cancers. The clusters of genes (modules) derived from a gastric cancer (GC) coexpression network were explored to understand their clinical and functional significance. Among the modules derived from the GC mRNA expression network, six modules were relatively highly expressed in diffuse type gastric tumours. Elevated expression of genes related to extracellular matrix (ECM), angiogenesis, collagen and intracellular cytoskeletal components and immune response were identified in these modules. ECM-related modules exhibited an inverse correlation with modules representing the expression of immune response genes. A reduced expression of immune response genes was identified as the key factor associated with the aggressive features of diffuse gastric tumours, which is indicative of tumour progression involving the escape from immune surveillance in diffuse tumours. A part of the identified aggressive factors was common between intestinal and diffuse type tumours. The coexpressed modules and their expression patterns delineate the fine transition involved in cancer progression in the later stages of tumours. The identified modules could serve as surrogate gene-sets, indicating the molecular staging of GC aggressiveness with underlying biological interaction.
Insights
This study explored gene expression in gastric cancer (GC), finding that diffuse type tumors show high expression of extracellular matrix and angiogenesis genes. Reduced immune response genes correlate with aggressive features, suggesting immune escape in diffuse GC.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Oncology
Background:
- Gene expression profiles offer insights into cancer molecular dysregulation.
- Gastric cancer (GC) subtypes exhibit distinct molecular characteristics.
Purpose of the Study:
- To explore the clinical and functional significance of gene modules in gastric cancer.
- To identify molecular drivers of aggressiveness in diffuse-type GC.
Main Methods:
- Analysis of gastric cancer mRNA expression data.
- Construction and exploration of gene coexpression networks.
- Identification and characterization of gene modules.
Main Results:
- Six gene modules were highly expressed in diffuse-type GC.
- Elevated expression of extracellular matrix (ECM), angiogenesis, and cytoskeletal genes identified.
- Inverse correlation between ECM-related modules and immune response genes.
- Reduced immune gene expression linked to aggressive diffuse GC features and immune escape.
- Shared aggressive factors between diffuse and intestinal types of GC.
Conclusions:
- Gene modules and expression patterns reveal transitions in late-stage tumor progression.
- Identified modules can serve as biomarkers for molecular staging of GC aggressiveness.
- Tumor progression in diffuse GC involves evading immune surveillance.