Transcriptomic analysis of autoimmune atrophic gastritis and type 1 gastric neuroendocrine tumours reveals concordant gene expression associated with mitochondrial dysfunction and epithelial reprogramming
Design: Autoimmune atrophic gastritis (AAG) is a chronic inflammatory disease characterized by parietal cell loss, hypochlorhydria, and hypergastrinemia, and represents a major risk factor for the development of type 1 gastric neuroendocrine tumours (G-NETs). The underlying molecular mechanisms in disease progression remain incompletely understood. Methods: Through RNA-sequencing we obtained a unique dataset comprising a well-characterised cohort of type 1 G-NET and AAG patients and compared these with control patient samples. Differential gene expression and pathway enrichment analyses were utilized to identify shared and disease-specific transcriptional signatures. Results: We found differentially expressed genes associated with mitochondrial function, metabolic pathways, epithelial remodelling, and immune signalling. While many gene expression patterns were shared between AAG and G-NET groups, G-NETs exhibited additional upregulation of neuroendocrine differentiation, extracellular matrix remodelling, and innate immune pathways, but AAG group showed pathway enrichment associated with absorption and metabolic functions. Conclusions: This study provides an in-depth transcriptomic view of disease progression within a well-characterized patient cohort revealing shared and distinct molecular mechanisms. Our findings highlight differentially expressed genes and shared pathways among the conditions, indicating mitochondrial dysfunction, metabolic and epithelial cell reprogramming, and distinct immune pathway engagement as central features of disease progression, offering potential targets for early detection and therapeutic intervention.
Design: Autoimmune atrophic gastritis (AAG) is a chronic inflammatory disease characterized by parietal cell loss, hypochlorhydria, and hypergastrinemia, and represents a major risk factor for the development of type 1 gastric neuroendocrine tumours (G-NETs). The underlying molecular mechanisms in disease progression remain incompletely understood. Methods: Through RNA-sequencing we obtained a unique dataset comprising a well-characterised cohort of type 1 G-NET and AAG patients and compared these with control patient samples. Differential gene expression and pathway enrichment analyses were utilized to identify shared and disease-specific transcriptional signatures. Results: We found differentially expressed genes associated with mitochondrial function, metabolic pathways, epithelial remodelling, and immune signalling. While many gene expression patterns were shared between AAG and G-NET groups, G-NETs exhibited additional upregulation of neuroendocrine differentiation, extracellular matrix remodelling, and innate immune pathways, but AAG group showed pathway enrichment associated with absorption and metabolic functions. Conclusions: This study provides an in-depth transcriptomic view of disease progression within a well-characterized patient cohort revealing shared and distinct molecular mechanisms. Our findings highlight differentially expressed genes and shared pathways among the conditions, indicating mitochondrial dysfunction, metabolic and epithelial cell reprogramming, and distinct immune pathway engagement as central features of disease progression, offering potential targets for early detection and therapeutic intervention.
Latvian Biomedical Research and Study Centre