Development of high-resolution melting analysis for ABCB1 promoter methylation: clinical consequences in breast and ovarian carcinoma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F75010330%3A_____%2F19%3A00012659" target="_blank" >RIV/75010330:_____/19:00012659 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11120/19:43918352 RIV/00216208:11130/19:10393569 RIV/00216208:11140/19:10393569 RIV/00064173:_____/19:N0000152 RIV/00064203:_____/19:10393569

Výsledek na webu

<a href="https://www.spandidos-publications.com/10.3892/or.2019.7186" target="_blank" >https://www.spandidos-publications.com/10.3892/or.2019.7186</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/or.2019.7186" target="_blank" >10.3892/or.2019.7186</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Development of high-resolution melting analysis for ABCB1 promoter methylation: clinical consequences in breast and ovarian carcinoma

Popis výsledku v původním jazyce

Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP-binding cassette (ABC) transporter P-glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high-resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression-free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.

Název v anglickém jazyce

Development of high-resolution melting analysis for ABCB1 promoter methylation: clinical consequences in breast and ovarian carcinoma

Popis výsledku anglicky

Multidrug resistance to anticancer drugs, which is often associated with enhanced expression of the ATP-binding cassette (ABC) transporter P-glycoprotein (encoded by the ABCB1 gene) may limit the effects of cancer therapy. Epigenetic regulation of ABCB1 expression may thus have a clinical impact. A detailed assessment of ABCB1 promoter methylation is of importance for predicting therapy outcome and prognosis. Thus, validated methods for the analysis of ABCB1 promoter methylation are urgently required. In the present study, high-resolution melting (HRM) analysis of the CpG island regions covering the distal promoter of the ABCB1 gene was developed and compared with pyrosequencing. In addition, the clinical effects of the methylation status of the ABCB1 promoter were analyzed in patients with breast and ovarian carcinoma prior and subsequent to chemotherapy treatment. HRM analysis of ABCB1 methylation correlated with the results of pyrosequencing (P=0.001) demonstrating its analytical validity and utility. Hypermethylation of the analyzed ABCB1 promoter region was significantly correlated with low levels of the ABCB1 transcript in tumors from a subset of patients with breast and ovarian carcinoma prior to chemotherapy but not following treatment. Finally, high ABCB1 transcript levels were observed in tumors of patients with short progression-free survival prior to chemotherapy. Our data suggest the existence of functional epigenetic changes in the ABCB1 gene with prognostic value in tumor tissues of patients with breast and ovarian carcinoma. The clinical importance of such changes should be further evaluated.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Oncology Reports

ISSN

1021-335X

e-ISSN

1791-2431

Svazek periodika

42

Číslo periodika v rámci svazku

2

Stát vydavatele periodika

GR - Řecká republika

Počet stran výsledku

12

Strana od-do

763-774

Kód UT WoS článku

000475611600026

EID výsledku v databázi Scopus

2-s2.0-85068222348