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Open AccessArticle

Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact

1
Laboratório de Medicina Genômica, Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
2
Programa de Pós-graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil
3
Programa de Carcinogênese Molecular, Instituto Nacional de Câncer, Rio de Janeiro 20231-050, Brazil
4
Instituto de Informática, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil
5
Núcleo de Bioinformática, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
6
Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro 21040-360, Brazil
7
Serviço de Patologia, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
8
Departamento de Patologia, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Brazil
9
Grupo de Vias Biliares e Pâncreas, Cirurgia do Aparelho Digestivo, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-007, Brazil
10
Programa de Pós-graduação em Medicina: Ciências Cirúrgicas, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
11
Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-007, Brazil
12
Departamento de Bioquimica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro 20550-900, Brazil
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(7), 1735; https://doi.org/10.3390/cancers12071735
Received: 29 April 2020 / Revised: 17 June 2020 / Accepted: 21 June 2020 / Published: 30 June 2020
(This article belongs to the Special Issue Targeting Calcium Signaling in Cancer Cells)
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with high mortality rates. PDAC initiation and progression are promoted by genetic and epigenetic dysregulation. Here, we aimed to characterize the PDAC DNA methylome in search of novel altered pathways associated with tumor development. We examined the genome-wide DNA methylation profile of PDAC in an exploratory cohort including the comparative analyses of tumoral and non-tumoral pancreatic tissues (PT). Pathway enrichment analysis was used to choose differentially methylated (DM) CpGs with potential biological relevance. Additional samples were used in a validation cohort. DNA methylation impact on gene expression and its association with overall survival (OS) was investigated from PDAC TCGA (The Cancer Genome Atlas) data. Pathway analysis revealed DM genes in the calcium signaling pathway that is linked to the key pathways in pancreatic carcinogenesis. DNA methylation was frequently correlated with expression, and a subgroup of calcium signaling genes was associated with OS, reinforcing its probable phenotypic effect. Cluster analysis of PT samples revealed that some of the methylation alterations observed in the Calcium signaling pathway seemed to occur early in the carcinogenesis process, a finding that may open new insights about PDAC tumor biology. View Full-Text
Keywords: pancreatic ductal adenocarcinoma; calcium signaling pathway; DNA methylation; early methylation alterations; prognostic biomarkers pancreatic ductal adenocarcinoma; calcium signaling pathway; DNA methylation; early methylation alterations; prognostic biomarkers
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Gregório, C.; Soares-Lima, S.C.; Alemar, B.; Recamonde-Mendoza, M.; Camuzi, D.; de Souza-Santos, P.T.; Rivero, R.; Machado, S.; Osvaldt, A.; Ashton-Prolla, P.; Pinto, L.F.R. Calcium Signaling Alterations Caused by Epigenetic Mechanisms in Pancreatic Cancer: From Early Markers to Prognostic Impact. Cancers 2020, 12, 1735.

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