Firma epigenética del cáncer cervical asociada a un exceso de peso determinada mediante un análisis bioinformático de metilación de regiones promotoras

• Autor: Oscanoa Aida, Rosa Maria
• Formato: tesis de maestría
• Fecha de Publicación: 2020
• Institución: Universidad Peruana Cayetano Heredia
• Repositorio: UPCH-Institucional
• Lenguaje: español
• OAI Identifier: oai:repositorio.upch.edu.pe:20.500.12866/8945
• Enlace del recurso: https://hdl.handle.net/20.500.12866/8945
• Nivel de acceso: acceso abierto
• Materia: Exceso de Peso; Metilación; Región Promotora; Cáncer Cervical; Sobrevida; CESC-TCGA; https://purl.org/pe-repo/ocde/ford#1.02.03; https://purl.org/pe-repo/ocde/ford#3.01.09; https://purl.org/pe-repo/ocde/ford#3.02.02; https://purl.org/pe-repo/ocde/ford#3.02.18

Introduction: Excess of body weight (overweight or obesity) is associated with the prognosis of cervical cancer (CCE) patients, however, the molecular mechanisms that explain this association remain unclear. The present study aimed to evaluate the potential association between excess of body weight, the methylation status of the promoter region of differentially expressed genes (DEGs) in CCE and overall survival. Methodology: We performed a secondary analysis of genomic and epigenomic data from the CCE free-access project, TCGA-CESC (The Cancer Genome Atlas Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma). Patients were classified according to their Body Mass Index (BMI) as patients without an excess of body weight (BMI<25) or patients with an excess of body weight (BMI≥25). We identified DEGs in CCE and retrieved expression level data using GEPIA and UCSC Xena, respectively. We selected DEGs with differential expression between the study groups, retrieved methylation level data through MethHC and evaluated the association between methylation in the promoter region and excess of body weight status. Additionally, we evaluated the association of clinical and demographic characteristics and the methylation status of the promoter region of eight selected DEGs. Finally, we evaluated the association between survival and methylation status of selected DEGs in CCE. Results: We identified 39 DEGs in CCE with significant differences in gene expression levels between patients with and without excess of body weight (p<0.01). A significant difference in methylation level of promoter region was observed between study groups in seven genes (p<0.05): SPOCK1 (NM_004598), EDIL3 (NM_005711), SEC31B (NM_015490), GPM6A (NM_005277), C2ORF40 (NM_032411), ETV7 (NM_016135) and MND1 (NM_032117). A significant association between FGF10 methylation status and excess of body weight status was evident [OR=3.81, 95% CI; 1.36-10.68], considering the rest of the clinical and demographic characteristics of the population constant. Finally, the methylation status of the under-expressed gene PRICKLE2 (NM_198859) was associated with overall survival (p=0.0022). Conclusion: We identified differences in the methylation level of the promoter region of seven DEGs in CCE according to excess of body weight status in the CESC-TCGA cohort. What is more, the methylation status of the under-expressed gene PRICKLE2 (NM_198859) was associated with overall survival. Our results suggest a role of methylation associated with excess of body weight in CCE and a possible implication in survival. This field of research is worth further exploration because of its potential clinical relevance.