<i>FBXL7</i> 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...
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2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/14/7801 |
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| author | Diego Camuzi Luisa Aguirre Buexm Simone de Queiroz Chaves Lourenço Rachele Grazziotin Simone Guaraldi Priscila Valverde Davy Rapozo Jill M. Brooks Hisham Mehanna Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima |
| author_facet | Diego Camuzi Luisa Aguirre Buexm Simone de Queiroz Chaves Lourenço Rachele Grazziotin Simone Guaraldi Priscila Valverde Davy Rapozo Jill M. Brooks Hisham Mehanna Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima |
| author_sort | Diego Camuzi |
| collection | DOAJ |
| 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 <i>FBXL7</i> 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 <i>FBXL7</i> gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. <i>FBXL7</i> 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 <i>FBXL7</i> body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker. |
| first_indexed | 2024-03-09T10:17:03Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T10:17:03Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-19894be4a4904029ae4a575d98fb810c2023-12-01T22:15:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012314780110.3390/ijms23147801<i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor ExposureDiego Camuzi0Luisa Aguirre Buexm1Simone de Queiroz Chaves Lourenço2Rachele Grazziotin3Simone Guaraldi4Priscila Valverde5Davy Rapozo6Jill M. Brooks7Hisham Mehanna8Luis Felipe Ribeiro Pinto9Sheila Coelho Soares-Lima10Molecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilMolecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilDepartment of Pathology, Dental School, Fluminense Federal University, Niterói 24040-110, BrazilMolecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilMolecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilPathology Division, National Cancer Institute, Rio de Janeiro 20230-130, BrazilPathology Division, National Cancer Institute, Rio de Janeiro 20230-130, BrazilInstitute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UKInstitute of Head and Neck Studies and Education (InHANSE), Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham B15 2TT, UKMolecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilMolecular Carcinogenesis Program, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, BrazilSquamous 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 <i>FBXL7</i> 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 <i>FBXL7</i> gene’s body is hypomethylated in the UADT, independently of histology, but not in virus-associated tumors. <i>FBXL7</i> 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 <i>FBXL7</i> body hypomethylation between non-tumor and tumor tissues makes it a promising biomarker.https://www.mdpi.com/1422-0067/23/14/7801DNA methylationcancersquamous cell carcinomaesophagushead and neckFBXL7 |
| spellingShingle | Diego Camuzi Luisa Aguirre Buexm Simone de Queiroz Chaves Lourenço Rachele Grazziotin Simone Guaraldi Priscila Valverde Davy Rapozo Jill M. Brooks Hisham Mehanna Luis Felipe Ribeiro Pinto Sheila Coelho Soares-Lima <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure International Journal of Molecular Sciences DNA methylation cancer squamous cell carcinoma esophagus head and neck FBXL7 |
| title | <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
| title_full | <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
| title_fullStr | <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
| title_full_unstemmed | <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
| title_short | <i>FBXL7</i> Body Hypomethylation Is Frequent in Tumors from the Digestive and Respiratory Tracts and Is Associated with Risk-Factor Exposure |
| title_sort | i fbxl7 i body hypomethylation is frequent in tumors from the digestive and respiratory tracts and is associated with risk factor exposure |
| topic | DNA methylation cancer squamous cell carcinoma esophagus head and neck FBXL7 |
| url | https://www.mdpi.com/1422-0067/23/14/7801 |
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