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FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure
Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with th...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316635/ https://www.ncbi.nlm.nih.gov/pubmed/35887149 http://dx.doi.org/10.3390/ijms23147801 |
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author | Camuzi, Diego Buexm, Luisa Aguirre Lourenço, Simone de Queiroz Chaves Grazziotin, Rachele Guaraldi, Simone Valverde, Priscila Rapozo, Davy Brooks, Jill M. Mehanna, Hisham Ribeiro Pinto, Luis Felipe Soares-Lima, Sheila Coelho |
author_facet | Camuzi, Diego Buexm, Luisa Aguirre Lourenço, Simone de Queiroz Chaves Grazziotin, Rachele Guaraldi, Simone Valverde, Priscila Rapozo, Davy Brooks, Jill M. Mehanna, Hisham Ribeiro Pinto, Luis Felipe Soares-Lima, Sheila Coelho |
author_sort | Camuzi, Diego |
collection | PubMed |
description | Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker. |
format | Online Article Text |
id | pubmed-9316635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93166352022-07-27 FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure Camuzi, Diego Buexm, Luisa Aguirre Lourenço, Simone de Queiroz Chaves Grazziotin, Rachele Guaraldi, Simone Valverde, Priscila Rapozo, Davy Brooks, Jill M. Mehanna, Hisham Ribeiro Pinto, Luis Felipe Soares-Lima, Sheila Coelho Int J Mol Sci Article Squamous cell carcinoma is the main histological tumor type in the upper aerodigestive tract (UADT), including the esophagus (ESCC) and the head and neck sites, as well as the oral cavity (OCSCC), larynx (LSCC) and oropharynx (OPSCC). These tumors are induced by alcohol and tobacco exposure, with the exception of a subgroup of OPSCC linked to human papillomavirus (HPV) infection. Few genes are frequently mutated in UADT tumors, pointing to other molecular mechanisms being involved during carcinogenesis. The F-box and leucine-rich repeat protein 7 (FBXL7) is a potential tumor-suppressing gene, one that is frequently hypermethylated in pancreatic cancer and where the encoded protein promotes the degradation of AURKA, BIRC5 and c-SRC. Thus, the aim of this study was to evaluate the methylation and expression profile of FBXL7 in the UADT and the gene’s association with the clinical, etiological and pathological characteristics of patients, as well as the expression of its degradation targets. Here we show that the FBXL7 gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. FBXL7 body methylation and gene expression levels were correlated in the ESCC, LSCC, OCSCC and OPSCC. Immunohistochemistry analysis showed that FBXL7 protein levels are not correlated with the levels of its degradation targets, AURKA and BIRC5, in the UADT. The high discriminatory potential of FBXL7 body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker. MDPI 2022-07-15 /pmc/articles/PMC9316635/ /pubmed/35887149 http://dx.doi.org/10.3390/ijms23147801 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Camuzi, Diego Buexm, Luisa Aguirre Lourenço, Simone de Queiroz Chaves Grazziotin, Rachele Guaraldi, Simone Valverde, Priscila Rapozo, Davy Brooks, Jill M. Mehanna, Hisham Ribeiro Pinto, Luis Felipe Soares-Lima, Sheila Coelho FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title | FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title_full | FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title_fullStr | FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title_full_unstemmed | FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title_short | FBXL7 Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
title_sort | fbxl7 body hypomethylation is frequent in tumors from the digestive and respiratory tracts and is associated with risk-factor exposure |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316635/ https://www.ncbi.nlm.nih.gov/pubmed/35887149 http://dx.doi.org/10.3390/ijms23147801 |
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