Portal de investigação
MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population
Data de publicação:
Data Ahead of Print:
Autores da FMUP
Participantes de fora da FMUP
- Almeida T.C.
- Macedo-Silva C.
- Costa J.
- Paulino S.
- Jerónimo C.
- Dinis-Ribeiro M.
- Pereira C.
Unidades de investigação
Abstract
Background: Early gastric cancer is treated endoscopically, but patients require surveillance due to the risk of metachronous gastric lesions (MGLs). Epigenetic alterations, particularly aberrant DNA methylation in genes, such as MIR124-3, MIR34b/c, NKX6-1, EMX1, MOS and CDO1, have been identified as promising biomarkers for MGL in Asian populations. We aimed to determine whether these changes could predict MGL risk in intermediate-risk Caucasian patients. Methods: This case–cohort study included 36 patients who developed MGL matched to 48 patients without evidence of MGL in the same time frame (controls). Multiplex quantitative methylation-specific PCR was performed using DNA extracted from the normal mucosa adjacent to the primary lesion. The overall risk of progression to MGL was assessed using Kaplan–Meier and Cox proportional hazards model analyses. Results: MIR124-3, MIR34b/c and NKX6-1 were successfully analyzed in 77 samples. MIR124-3 hypermethylation was detected in individuals who developed MGL (relative quantification 78.8 vs 50.5 in controls, p = 0.014), particularly in females and Helicobacter pylori-negative patients (p = 0.021 and p = 0.0079, respectively). This finding was further associated with a significantly greater risk for MGL development (aHR = 2.31, 95% CI 1.03–5.17, p = 0.042). Similarly, NKX6-1 was found to be hypermethylated in patients with synchronous lesions (relative quantification 7.9 vs 0.0 in controls, p = 0.0026). A molecular-based methylation model incorporating both genes was significantly associated with a threefold increased risk for MGL development (aHR = 3.10, 95% CI 1.07–8.95, p = 0.037). Conclusions: This preliminary study revealed an association between MIR124-3 and NKX6-1 hypermethylation and the development of MGL in a Western population. These findings may represent a burden reduction and a greener approach to patient care. © The Author(s) 2024.
© 2024. The Author(s).
Dados da publicação
- ISSN/ISSNe:
- 1868-7083, 1868-7075
- Tipo:
- Article
- Páginas:
- 113-113
- Link para outro recurso:
- www.scopus.com
Clinical Epigenetics BioMed Central Ltd.
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Filiações
Keywords
- Aged; Biomarkers, Tumor; Case-Control Studies; DNA Methylation; Epigenesis, Genetic; Female; Homeodomain Proteins; Humans; Male; MicroRNAs; Middle Aged; Neoplasms, Second Primary; Stomach Neoplasms; White People; homeodomain protein; microRNA; NKX6-1 protein, human; tumor marker; adult; aged; Article; cancer growth; cancer risk; carcinogenesis; Caucasian; clinical article; clinical assessment; cohort analysis; controlled study; DNA extraction; epigenetics; ethnic difference; evidence based practice; female; genetic analysis; genetic association; Helicobacter pylori; human; male; middle aged; MIR124 3 gene; multiplex real time polymerase chain reaction; NKX6 1 gene; nonhuman; oncogene; patient care; patient selection; population research; population structure; prediction; RNA fingerprinting; RNA methylation; second cancer; sex difference; stomach cancer; tumor burden; case control study; DNA methylation; genetic epigenesis; genetics; second primary neoplasm; stomach tumor
Campos de estudo
Financiamento
Proyectos asociados
Tracking the acquisition of eating habits in children and its effects on behaviours related to appetite
Investigador Principal: Carla Maria de Moura Lopes
Estudo Clínico Académico . 2019
Citar a publicação
Lopes C,Almeida TC,Macedo C,Costa J,Paulino S,Jerónimo C,Libânio D,Dinis M,Pereira C. MIR124-3 and NKX6-1 hypermethylation profiles accurately predict metachronous gastric lesions in a Caucasian population. Clin. Epigenetics. 2024. 16. (1):p. 113-113. IF:5,700. (1).
