title: hsa-miR-29c and hsa-miR-135b differential expression as potential biomarker of gastric carcinogenesis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Amanda Ferreira
authors.initials: AF
authors.lastname: Vidal
authors.affiliation: 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.
authors.forename: Aline M P
authors.initials: AM
authors.lastname: Cruz
authors.affiliation: 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.
authors.forename: Leandro
authors.initials: L
authors.lastname: Magalhães
authors.affiliation: 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.
authors.forename: Adenilson L
authors.initials: AL
authors.lastname: Pereira
authors.affiliation: 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.
authors.forename: Ana K M
authors.initials: AK
authors.lastname: Anaissi
authors.affiliation: 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.
authors.forename: Nélisson C F
authors.initials: NC
authors.lastname: Alves
authors.affiliation: 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.
authors.forename: Paulo J B S
authors.initials: PJ
authors.lastname: Albuquerque
authors.affiliation: 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.
authors.forename: Rommel M R
authors.initials: RM
authors.lastname: Burbano
authors.affiliation: 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.
authors.forename: Samia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: 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.
authors.forename: Ândrea
authors.initials: Â
authors.lastname: Ribeiro-dos-Santos
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000235:genetics*; D063646:Carcinogenesis / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D000090205:DNA Methyltransferase 3A; D044127:Epigenesis, Genetic; D005753:Gastric Mucosa / Q000737:chemistry / Q000473:pathology; D005757:Gastritis, Atrophic / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D008679:Metaplasia; D035683:MicroRNAs / Q000235:genetics*; D011237:Predictive Value of Tests; D012372:ROC Curve; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; D014408:Biomarkers, Tumor; C000717967:DNMT3A protein, human; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C544965:MIRN135 microRNA, human; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A
keywords: Biomarker; Carcinogenesis; Gastric cancer; Gastric lesions; MicroRNA