title: High-Throughput miRNA Sequencing Reveals a Field Effect in Gastric Cancer and Suggests an Epigenetic Network Mechanism.
abstract: Field effect in cancer, also called "field cancerization", attempts to explain the development of multiple primary tumors and locally recurrent cancer. The concept of field effect in cancer has been reinforced, since molecular alterations were found in tumor-adjacent tissues with normal histopatho-logical appearances. With the aim of investigating field effects in gastric cancer (GC), we conducted a high-throughput sequencing of the miRnome of four GC samples and their respective tumor-adjacent tissues and compared them with the miRnome of a gastric antrum sample from patients without GC, assuming that tumor-adjacent tissues could not be considered as normal tissues. The global number of miRNAs and read counts was highest in tumor samples, followed by tumor-adjacent and normal samples. Analyzing the miRNA expression profile of tumor-adjacent miRNA, hsa-miR-3131, hsa-miR-664, hsa-miR-483, and hsa-miR-150 were significantly downregulated compared with the antrum without tumor tissue (P-value < 0.01; fold-change <5). Additionally, hsa-miR-3131, hsa-miR-664, and hsa-miR-150 were downregulated (P-value < 0.001) in all paired samples of tumor and tumor-adjacent tissues, compared with antrum without tumor mucosa. The field effect was clearly demonstrated in gastric carcinogenesis by an epigenetics-based approach, and potential biomarkers of the GC field effect were identified. The elevated expression of miRNAs in adjacent tissues and tumors tissues may indicate that a cascade of events takes place during gastric carcinogenesis, reinforcing the notion of field effects. This phenomenon seems to be linked to DNA methylation patterns in cancer and suggests the involvement of an epigenetic network mechanism.
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Monica B
authors.initials: MB
authors.lastname: Assumpção
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Centro Universitário do Estado do Pará, Belém, Pará, Brazil.
authors.forename: Fabiano C
authors.initials: FC
authors.lastname: Moreira
authors.affiliation: Universidade Federal Rural da Amazônia, Capanema, PA, Brazil.
authors.forename: Igor G
authors.initials: IG
authors.lastname: Hamoy
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Magalhães
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Vidal
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Adenilson
authors.initials: A
authors.lastname: Pereira
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Rommel
authors.initials: R
authors.lastname: Burbano
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Khayat
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Artur
authors.initials: A
authors.lastname: Silva
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Sidney
authors.initials: S
authors.lastname: Santos
authors.affiliation: Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil. ; Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Ândrea
authors.initials: Â
authors.lastname: Ribeiro-Dos-Santos
authors.affiliation: Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA, Brazil. ; Núcleo de Pesquisa em Oncologia, Universidade Federal do Pará, Belém, PA, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Assumpção
keywords: epigenetic; field effect; gastric cancer; high-throughput sequencing; miRNA; miRnome