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©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis
Amanda Ferreira Vidal, Aline MP Cruz, Leandro Magalhães, Adenilson L Pereira, Ana KM Anaissi, Nélisson CF Alves, Paulo JBS Albuquerque, Rommel MR Burbano, Samia Demachki, Ândrea Ribeiro-dos-Santos
Amanda Ferreira Vidal, Aline MP Cruz, Leandro Magalhães, Adenilson L Pereira, Ana KM Anaissi, Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Pará, Cidade Universitária Prof. José Silveira Netto, Belém, PA 66075-970, Brasil
Amanda Ferreira Vidal, Aline MP Cruz, Leandro Magalhães, Adenilson L Pereira, Ana KM Anaissi, Ândrea Ribeiro-dos-Santos, Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA 66075-970, Brasil
Nélisson CF Alves, Pós-Graduação em Neurociências e Biologia Molecular, Universidade Federal do Pará, Belém, PA 66075-970, Brasil
Nélisson CF Alves, Rommel MR Burbano, Laboratório de Citogenética Humana- Instituto de Ciências Biológicas, Universidade Federal do Pará, Belém, PA 66075-970, Brasil
Paulo JBS Albuquerque, Hospital São Camilo e São Luís - Rua Dr. Marcelo Cândia, Macapá, AP 68901-901, Brasil
Rommel MR Burbano, Samia Demachki, Ândrea Ribeiro-dos-Santos, Núcleo de Pesquisas em Oncologia, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, PA 66075-970, Brasil
Samia Demachki, Instituto de Ciências da Saúde, Universidade Federal do Pará, Belém, PA 66075-970, Brasil
Author contributions: Vidal AF performed the experiments, analyzed the data and wrote the manuscript; Cruz AMP performed the experiments; Magalhães L performed the statistical analysis and reviewed the manuscript; Anaissi AKM, Alves NCF, Albuquerque PJBS, Burbano RMR and Demackhi S selected samples and obtained the clinical and pathological informations; Ribeiro-dos-Santos A conceived of the study, and participated in its design and coordination; all authors approved the final version of manuscript.
Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico; Fundação Amazônia Paraense de Amparo a Pesquisa; and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/Bio Computacional, No. 3381/2013.
Institutional review board statement: The study was reviewed and approved by Local Ethics Committee (protocol number: 657 666) in accordance with the Helsinki Declaration of 1964.
Informed consent statement: All study participants or their legal guardian provided informed written consent in accordance with the Helsinki Declaration of 1964.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Ândrea Ribeiro-dos-Santos, Laboratório de Genética Humana e Médica, Instituto de Ciências Biológicas, Universidade Federal do Pará, Av. Augusto Corrêa 01, Belém, PA 66075-970, Brasil. akelyufpa@gmail.com
Telephone: +55-91-32017843 Fax: +55-91-32017843
Received: June 23, 2015
Peer-review started: June 26, 2015
First decision: August 26, 2015
Revised: September 10, 2015
Accepted: November 13, 2015
Article in press: November 13, 2015
Published online: February 14, 2016
AIM: To investigate the expression profiles of hsa-miR-29c and hsa-miR-135b in gastric mucosal samples and their values as gastric carcinogenesis biomarkers.
METHODS: The expression levels of hsa-miR-29c and hsa-miR-135b in normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinal-type gastric adenocarcinoma were analysed using quantitative real-time PCR. The difference between hsa-miR-29c and hsa-miR-135b expression profiles in the grouped samples was evaluated by ANOVA and Student’s t-test tests. The results were adjusted for multiple testing by using Bonferroni’s correction. P values ≤ 0.05 were considered statistically significant. To evaluate hsa-miR-29c and hsa-miR-135b expressions as potential biomarkers of gastric carcinogenesis, we performed a receiver operating characteristic curve analysis and the derived area under the curve, and a Categorical Principal Components Analysis. In silico identification of the genetic targets of hsa-miR-29c and hsa-miR-135b was performed using different prediction tools, in order to identify possible genes involved in gastric carcinogenesis.
RESULTS: The expression levels of hsa-miR-29c were higher in normal gastric mucosal samples, and decreased progressively in non-atrophic chronic gastritis samples, intestinal metaplasia samples and intestinal-type gastric adenocarcinoma samples. The expression of hsa-miR-29c in the gastric lesions showed that non-atrophic gastritis have an intermediate profile to gastric normal mucosa and intestinal-type gastric adenocarcinoma, and that intestinal metaplasia samples presented an expression pattern similar to that in intestinal-type gastric adenocarcinoma. This microRNA (miRNA) has a good discriminatory accuracy between normal gastric samples and (1) intestinal-type gastric adenocarcinoma; and (2) intestinal metaplasia, and regulates the DMNT3A oncogene. hsa-miR-135b is up-regulated in non-atrophic chronic gastritis and intestinal metaplasia samples and down-regulated in normal gastric mucosa and intestinal-type gastric adenocarcinoma samples. Non-atrophic chronic gastritis and intestinal metaplasia are significantly different from normal gastric mucosa samples. hsa-miR-135b expression presented a greater discriminatory accuracy between normal samples and gastric lesions. This miRNA was associated with Helicobacter pylori presence in non-atrophic chronic gastritis samples and regulates the APC and KLF4 tumour suppressor genes.
CONCLUSION: Our results provide evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-miR-29c and hsa-miR-135b are promising biomarkers of gastric carcinogenesis.
Core tip: The miRNAs hsa-miR-29c and hsa-miR-135b were reported as potential biomarkers of intestinal-type gastric adenocarcinoma. We evaluated and compared the expression profile of these miRNAs in gastric mucosal samples, including normal gastric mucosa, non-atrophic chronic gastritis, intestinal metaplasia and intestinal-type gastric adenocarcinoma. Our results provided evidence of epigenetic alterations in non-atrophic chronic gastritis and intestinal metaplasia and suggest that hsa-miR-29c and hsa-miR-135b are promising biomarkers of gastric carcinogenesis.
