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HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC...

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Autores principales: Lima, Erika Urbano, Rubio, Ileana G S, Da Silva, Joaquim Custodio, Galrão, Ana Luiza, Pêssoa, Danielle, Oliveira, Taise Cerqueira, Carrijo, Fabiane, Silva Campos, Igor, Fonseca Espinheira, Luciano, Sampaio, Luiz Jose, Lima, Claudio Rogerio, Cerutti, Janete Maria, Ramos, Helton Estrela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280589/
https://www.ncbi.nlm.nih.gov/pubmed/30400039
http://dx.doi.org/10.1530/EC-18-0380
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author Lima, Erika Urbano
Rubio, Ileana G S
Da Silva, Joaquim Custodio
Galrão, Ana Luiza
Pêssoa, Danielle
Oliveira, Taise Cerqueira
Carrijo, Fabiane
Silva Campos, Igor
Fonseca Espinheira, Luciano
Sampaio, Luiz Jose
Lima, Claudio Rogerio
Cerutti, Janete Maria
Ramos, Helton Estrela
author_facet Lima, Erika Urbano
Rubio, Ileana G S
Da Silva, Joaquim Custodio
Galrão, Ana Luiza
Pêssoa, Danielle
Oliveira, Taise Cerqueira
Carrijo, Fabiane
Silva Campos, Igor
Fonseca Espinheira, Luciano
Sampaio, Luiz Jose
Lima, Claudio Rogerio
Cerutti, Janete Maria
Ramos, Helton Estrela
author_sort Lima, Erika Urbano
collection PubMed
description BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). PATIENTS AND METHODS: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. RESULTS: HOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. CONCLUSION: A moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients.
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spelling pubmed-62805892018-12-10 HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance Lima, Erika Urbano Rubio, Ileana G S Da Silva, Joaquim Custodio Galrão, Ana Luiza Pêssoa, Danielle Oliveira, Taise Cerqueira Carrijo, Fabiane Silva Campos, Igor Fonseca Espinheira, Luciano Sampaio, Luiz Jose Lima, Claudio Rogerio Cerutti, Janete Maria Ramos, Helton Estrela Endocr Connect Research BACKGROUND: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). PATIENTS AND METHODS: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. RESULTS: HOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. CONCLUSION: A moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients. Bioscientifica Ltd 2018-10-24 /pmc/articles/PMC6280589/ /pubmed/30400039 http://dx.doi.org/10.1530/EC-18-0380 Text en © 2018 The authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Research
Lima, Erika Urbano
Rubio, Ileana G S
Da Silva, Joaquim Custodio
Galrão, Ana Luiza
Pêssoa, Danielle
Oliveira, Taise Cerqueira
Carrijo, Fabiane
Silva Campos, Igor
Fonseca Espinheira, Luciano
Sampaio, Luiz Jose
Lima, Claudio Rogerio
Cerutti, Janete Maria
Ramos, Helton Estrela
HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title_full HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title_fullStr HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title_full_unstemmed HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title_short HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance
title_sort hopx homeobox methylation in differentiated thyroid cancer and its clinical relevance
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6280589/
https://www.ncbi.nlm.nih.gov/pubmed/30400039
http://dx.doi.org/10.1530/EC-18-0380
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