BioProject

Purpose: Celiac disease (CD) is a risk factor for developing Small Bowel Carcinoma (SBC) with a 14 folds higher risk than that of the general population. More...

Purpose: Celiac disease (CD) is a risk factor for developing Small Bowel Carcinoma (SBC) with a 14 folds higher risk than that of the general population. As SBCs associated with CD (CD-SBCs) are extremely rare, very few molecular data are currently available about their pathogenesis and information about CD-SBC transcriptomic profiling is completely lacking. Patients and Methods: We generated RNA-seq data on 13 CD-SBCs selected from the largest and well-characterized series of CD-SBCs published so far that was collected by the Small Bowel Cancer Italian Consortium. In all cases we compared the CD-SBC transcriptional signatures with the four consensus molecular subtypes (CMS) of colorectal carcinoma (CRC) applying the ‘CMS classifier’. CpG Island Methylator Phenotype (CIMP+) was evaluated in all cases using methylation-sensitive multiple ligation-dependent probe amplification. Results: RNA-based signatures of CD-SBCs exhibited strong similarities with CRCs. Twelve of 13 CD-SBCs (92%) fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e. CMS1 and CMS4. CMS1 CD-SBCs (62% of cases) were commonly MSI/CIMP+ tumors and showed increased expression of genes associated with a diffuse TH1 and cytotoxic T immune infiltrate, up-regulation of apoptosis, cell cycle progression and proteasome pathways. CMS4 CD-SBCs (31% of cases) showed prominent TGF-β activation and were characterized by complement-associated inflammation, matrix remodeling, stromal invasion and angiogenesis Conclusions: RNA-based signatures of CD-SBCs strongly recapitulate CMS classification of CRC, give a promising tool to improve our knowledge of this rare entity and provide clinically useful information using the wealth of data available for CRC. Less...