Identification new biomarkers for neoplasticprogression in ulcerative colitis to colorectal cancer

Background: In recent studies, the void of evaluation and indepthunderstanding of unknown clinically relevant potentialmolecular biomarkers involved in colorectal cancer (CRC)from the inflammatory stage of ulcerative colitis (UC) to CRCmetastasis, which can be suitable therapeutic targets, is deeplyfelt. The regulation and interaction among different cancer-promotingmolecules, including messenger RNAs (mRNAs) andmicro RNAs (miRNAs) in CRC and its progression, were theaim we pursued in this study.Materials and Methods: Using microarray data, we investigatedthe differential expression for five datasets, includingmRNA and microRNA samples related to UC, tumor/normal.Then, using robust data analysis, separate lists of differentiallyexpressed genes (DEGs) and differentially expressed miRNAs(DE miRNAs) were identified, which were used for robust rankaggregation (RRA) and co-expression network analysis. Then,comprehensive computational systems biology analyses, includinggene ontology and Kyoto encyclopedia of genes andgenomic pathway enrichment analyses, mRNA-miRNA regulatorynetwork, and survival analysis, were employed to achievethe aim of this study. Finally, we used clinical samples to validatethis potential and new target.Results: According to this systems biology approach, a total of۹۸ DEGs and ۸ DEmiRNAs with common differential expressionwere identified. By combining the distinct results of RRAand network, several potential therapeutic targets, and predictiveand prognostic biomarkers for UC and CRC were identified.These targets include six common hub genes, CXCL۱, CXCL۸,MMP۷, SLCA۱۶A۹, PLAU, and TIMP۱, which are upregulated.Among these, the important and new biomarker SLC۱۶A۹is negatively regulated by mir-۱۹۴-۵p, and miR-۳۷۸a-۵p take.Conclusion: The findings of the present study provide new insightinto the pathogenesis of CRC in UC. Our study suggestsfuture evaluation of the functional role of SLC۱۶A۹ and mir-۱۹۴-۵p and miR-۳۷۸a-۵p in CRC development

کلیدواژه ها:

Colorectal cancer ، ulcerative colitis ، miRNA ، Biomarker ، Systems biology