Microbiome and Molecular Characterization of Neoplasms in Pancreas and Intestine

This thesis has attempted to demonstrate microbiome and molecular characterizations of neoplasms in the pancreas and intestine. It has become well established that alterations in the abundance and diversity of bacterial species, can lead to the development of premalignant and malignant lesions in the human stomach, colon, and rectum. However, detection of microbes or microbial components in pancreatic neoplasms has not yet been performed. In this thesis, we investigate the microbial profiles of pancreatic cyst fluid and show a tantalizing possibility that pancreatic neoplasms, like Helicobacter Pylori-induced gastric neoplasms, are probably a bacteria-induced disease. Furthermore, we review and provide insights into links between spatial organization of microbial communities, so-called biofilms, and their contribution to CRC initiation and development. We propose that aggregation and collaboration of multiple microbial species in biofilms appear to have an increased potential to promote mucus secretion in colonic tumor cells. Moreover, we have evaluated previously reported mechanisms and identified new players to stabilize the ATOH1 protein, one of the main transcriptional factors to regulate mucinous differentiation in the gastrointestinal tract. In addition, we investigate the relevance of specific truncating RNF43 mutations for the tumorigenic process. Lastly, integrating the microbiome and molecular characterizations of neoplasms, I discuss the interplay between the microbiome, host genetic variations and DNA mutations acquired during tumorigenesis. The findings and speculations in this thesis may help shed light into the etiology of digestive cancers.

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