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

Abstract

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.

Catenin Alpha-2 Mutation Changes the Immune Microenvironment in Lung Adenocarcinoma Patients Receiving Immune Checkpoint Inhibitors

“…Furthermore, the gene levels of a disintegrin and metalloprotease 23 (ADAM23) in central memory B cells, Fc fragment of IgA receptor (FCAR) and L1 cell adhesion molecule (L1CAM) in macrophages, adenylate cyclase activating polypeptide 1 (ADCYAP1) and sialic acid binding Ig-like lectin 6 (SIGLEC6) in mast cells, and GATA binding protein 3 (GATA3) in Th2 cells were found to increase ( Figure 2D ). Among them, ADAM23 is considered to be a possible tumor suppressor gene and is often downregulated in various malignant tumors ( Zmetakova et al, 2019 ). In addition, we used the cancer testis antigen (CTA) immune scoring system to score CTNNA2-WT and CTNNA2-MT LUAD patients in the LUAD cohort of TCGA (see Materials and Methods ).…”

Genome-wide association study for mammary structure in Canadian Angus cows

“…Verbisck et al [ 29 ] demonstrated that cancer cells not expressing ADAM23 had higher migration capacities. Thus, the gene has been associated with multiple types of cancer, including breast cancers [ 30 , 31 ]. In addition, Elizondo et al [ 32 ] have demonstrated ADAM23 involvement in immune function has the expression of ADAM23 in dendritic cells governs T cell proliferation and cytokine production.…”

“…Verbisck et al [29] demonstrated that cancer cells not expressing ADAM23 had higher migration capacities. Thus, the gene has been associated with multiple types of cancer, including breast cancers [30,31]. In addition, Elizondo et al [32] have demonstrated https://doi.org/10.1371/journal.pone.0237818.g003…”

Prognostic value of tumour microenvironment‐related genes by TCGA database in rectal cancer

“…A disintegrin and metalloprotease 23 ( ADAM23 ), a member of the ADAM family, is considered a possible tumour suppressor gene, 36 and is frequently down‐regulated in various types of malignancies 37,38 . The silencing or decreased methylation of ADAM23 gene often associated with advanced disease and metastasis in different types of tumours, 39,40 including colorectal cancer 41 .…”