Coexpressed modular gene expression reveals inverse correlation between immune responsive transcription and aggressiveness in gastric tumours

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.

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