Associação entre ritmo circardiano, câncer e diabetes utilizando ferramentas da bioinformática

Abstract

Introduction: Tumorigenesis is affected by clock genes. Changes in the expression of clock genes can increase cancer susceptibility through the effects on biological mechanisms that regulate DNA damage and repair, energy metabolism, cell growth and death in neoplastic tissues Objective: to analyze the association of circadian rhythm, type 2 diabetes and cancer. Methodology: The study is a meta-analysis performed on type 2 diabetes, genes related to circadian rhythm and transcriptome data associated with breast, bladder, liver, pancreas, colon and rectum cancer using the integration of gene expression profiles with biomolecular in genome scale networks in diabetes samples, the databases searched were Pubmed and TCGA. The descriptors circadian rhythm, type 2 diabetes and cancer in English were used with Boolean operators and or or. Results: several common genes deregulate in diabetes mellitus and cancer. KLF10, NTKR3, IGF1, USP2, EZH2 were both down-regulated in samples of type 2 diabetes and cancer, while ARNTL2 AND AGRP were up-regulated. It appears that changes in mRNA are contributing to phenotypic changes in type 2 diabetes, resulting in phenotypic changes associated with malignant transformation. Taking these genes to perform a survival analysis, we found only the IGF1, USP2 and ARNTL2 genes associated with patient results. While negative regulation of IGF1 and USP2 had a negative impact, positive regulation of ARNTL2 was associated with poor survival in BLCA and BRCA cancer samples. Conclusion: These biological molecules not only represent the association of type 2 diabetes and circadian rhythm biomarkers with breast, bladder, liver, colon and rectum cancer, but also have significant potential to be considered as system-level biomarkers that can be used for screening or therapeutic purposes.