A disintegrin and metalloprotease 23 hypermethylation predicts decreased disease‐free survival in low‐risk breast cancer patients

Autor: Tatiana Sedlackova, Martin Bohac, Marina Cihova, Bozena Smolkova, Verona Buocikova, Marian Karaba, Ludovit Danihel, Gabriel Minarik, Juraj Benca, Iveta Zmetakova, Ivana Fridrichova, Michal Mego, Svetlana Miklikova, Zuzana Cierna, Viera Horvathova Kajabova, Lenka Kalinkova
Rok vydání: 2019
Předmět:
0301 basic medicine
Cancer Research
Epithelial-Mesenchymal Transition
Tumor suppressor gene
hematogenous dissemination
Down-Regulation
Ki-1 Antigen
Breast Neoplasms
Disease-Free Survival
Epigenesis
Genetic
03 medical and health sciences
breast cancer
0302 clinical medicine
Circulating tumor cell
mesenchymal circulating tumor cell
Clinical Research
Biomarkers
Tumor
medicine
Humans
Promoter Regions
Genetic
business.industry
Mesenchymal stem cell
ADAM23
Cancer
Original Articles
ADAM23 gene
Sequence Analysis
DNA
General Medicine
Methylation
DNA Methylation
Neoplastic Cells
Circulating
Prognosis
medicine.disease
Gene Expression Regulation
Neoplastic
ADAM Proteins
030104 developmental biology
Oncology
030220 oncology & carcinogenesis
DNA methylation
SNAI1
Cancer research
Original Article
Female
disease‐free survival
business
Zdroj: Cancer Science
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.13985
Popis: A Disintegrin And Metalloprotease 23 (ADAM23), a member of the ADAM family, is involved in neuronal differentiation and cancer. ADAM23 is considered a possible tumor suppressor gene and is frequently downregulated in various types of malignancies. Its epigenetic silencing through promoter hypermethylation was observed in breast cancer (BC). In the present study, we evaluated the prognostic significance of ADAM23 promoter methylation for hematogenous spread and disease-free survival (DFS). Pyrosequencing was used to quantify ADAM23 methylation in tumors of 203 BC patients. Presence of circulating tumor cells (CTC) in their peripheral blood was detected by quantitative RT-PCR. Expression of epithelial (KRT19) or mesenchymal (epithelial-mesenchymal transition [EMT]-inducing transcription factors TWIST1, SNAI1, SLUG and ZEB1) mRNA transcripts was examined in CD45-depleted peripheral blood mononuclear cells. ADAM23 methylation was significantly lower in tumors of patients with the mesenchymal CTC (P = .006). It positively correlated with Ki-67 proliferation, especially in mesenchymal CTC-negative patients (P = .001). In low-risk patients, characterized by low Ki-67 and mesenchymal CTC absence, ADAM23 hypermethylation was an independent predictor of DFS (P = .006). Our results indicate that ADAM23 is likely involved in BC progression and dissemination of mesenchymal CTC. ADAM23 methylation has the potential to function as a novel prognostic marker and therapeutic target.
Databáze: OpenAIRE
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