Open AccessA disintegrin and metalloprotease 23 hypermethylation predicts decreased disease‐free survival in low‐risk breast cancer patients
Author(s) -
Zmetakova Iveta,
Kalinkova Lenka,
Smolkova Bozena,
Horvathova Kajabova Viera,
Cierna Zuzana,
Danihel Ludovit,
Bohac Martin,
Sedlackova Tatiana,
Minarik Gabriel,
Karaba Marian,
Benca Juraj,
Cihova Marina,
Buocikova Verona,
Miklikova Svetlana,
Mego Michal,
Fridrichova Ivana
Publication year - 2019
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13985
Subject(s) - cancer research , dna methylation , breast cancer , methylation , epithelial–mesenchymal transition , cancer , circulating tumor cell , tumor progression , pathology , medicine , oncology , metastasis , chemistry , gene expression , gene , biochemistry
A Disintegrin And Metalloprotease 23 ( ADAM 23), a member of the ADAM family, is involved in neuronal differentiation and cancer. ADAM 23 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 ADAM 23 promoter methylation for hematogenous spread and disease‐free survival ( DFS ). Pyrosequencing was used to quantify ADAM 23 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 ( KRT 19 ) or mesenchymal ( epithelial‐mesenchymal transition [EMT] ‐inducing transcription factors TWIST 1 , SNAI 1 , SLUG and ZEB 1 ) mRNA transcripts was examined in CD 45‐depleted peripheral blood mononuclear cells. ADAM 23 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, ADAM 23 hypermethylation was an independent predictor of DFS ( P = .006). Our results indicate that ADAM 23 is likely involved in BC progression and dissemination of mesenchymal CTC . ADAM 23 methylation has the potential to function as a novel prognostic marker and therapeutic target.