A duodenal mucosa transcriptome study identified reduced expression of a novel gene CDH18 in celiac disease

Abstract

Background: Celiac disease (CD) a complex immune disease that affects duodenal mucosa. Identification of tissue specific biomarkers is expected to improve the existing biopsy based CD diagnosis.

Aims: To investigate the differentially expressed genes (DEGs) in duodenal mucosa tissue to identify clinically relevant gene expression pattern in CD.

Methods: Whole RNA extracted from the duodenal biopsies of three CD patients and four non-CD controls were sequenced. Significant DEGs were identified. Prioritized DEGs were validated using qRT-PCR in an independent group (CD=23; Control=26). Enriched pathways were analyzed, protein-protein interaction networks were evaluated.

Results: 923 DEGs comprising of 135 up-regulated, and 788 down-regulated genes, with p-value≤0.05; log2FC>2 or <-2 were identified. A novel down-regulated gene CDH18 (p = 0.03; log2FC=-0.74) was identified. Previously known CXCL9 was replicated. CDH18, a trans-membrane protein was found to interact with other CDH proteins, α/β catenins, and other membrane transporters such as SLC and ABCB. Pathways and protein networks contributing in channel activity (p = 2.15E-12), membrane transporters (p = 2.15E-12), and cellular adhesion (p = 8.05E-6) were identified.

Conclusions: CDH18, a novel DEG identified in the present study is a pivotal gene involved in maintaining epithelial membrane organization and integrity. The functional significance of lower expression of CDH18 in pathogenesis of CD warranted to be investigated. CDH18 expression could be tested for its effectiveness in diagnostic, prognostic and therapeutic purposes.

Keywords: CDH18; Celiac disease; Differential expression; Duodenal mucosa; RNA sequencing; qRT-PCR.