Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/39097 http://dx.doi.org/10.1186/s12916-015-0350-3 |
Resumo: | Background: the presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients.Methods: An initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. the most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. the accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values.Results: Seven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined.Conclusions: the high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance. |
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Carvalho, Ana Carolina de [UNIFESP]Scapulatempo-Neto, CristovamMaia, Danielle Calheiros Campelo [UNIFESP]Evangelista, Adriane FeijoMorini, Mariana AndoziaCarvalho, Andre LopesVettore, Andre Luiz [UNIFESP]Universidade Federal de São Paulo (UNIFESP)Barretos Canc HospDuke NUS Grad Med Sch2016-01-24T14:40:30Z2016-01-24T14:40:30Z2015-05-09Bmc Medicine. London: Biomed Central Ltd, v. 13, 14 p., 2015.1741-7015http://repositorio.unifesp.br/handle/11600/39097http://dx.doi.org/10.1186/s12916-015-0350-3WOS000354935300001.pdf10.1186/s12916-015-0350-3WOS:000354935300001Background: the presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients.Methods: An initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. the most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. the accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values.Results: Seven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined.Conclusions: the high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Dept Biol Sci, Lab Canc Mol Biol, BR-04039032 São Paulo, SP, BrazilBarretos Canc Hosp, Mol Oncol Res Ctr, BR-14784400 Barretos, SP, BrazilBarretos Canc Hosp, Dept Pathol, BR-14784400 Barretos, SP, BrazilBarretos Canc Hosp, Dept Head & Neck Surg, BR-14784400 Barretos, SP, BrazilDuke NUS Grad Med Sch, Canc Stem Cell Biol Program, Singapore 169857, SingaporeUniversidade Federal de São Paulo, Dept Biol Sci, Lab Canc Mol Biol, BR-04039032 São Paulo, SP, BrazilFAPESP: 2012/14837-7Web of Science14engBiomed Central LtdBmc MedicineDiagnostic markersFine-needle aspiration biopsiesHead and neck cancersMicroRNAsmiR-200 familymiR-203miR-205Neck metastasesAccuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinomainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000354935300001.pdfapplication/pdf1744870${dspace.ui.url}/bitstream/11600/39097/1/WOS000354935300001.pdfe3507d8cfc9365df3ecb4a83f668b2eeMD51open accessTEXTWOS000354935300001.pdf.txtWOS000354935300001.pdf.txtExtracted texttext/plain57017${dspace.ui.url}/bitstream/11600/39097/2/WOS000354935300001.pdf.txtf864757577254383527d301f5a1725f1MD52open access11600/390972022-09-27 12:00:39.359open accessoai:repositorio.unifesp.br:11600/39097Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-09-27T15:00:39Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
title |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
spellingShingle |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma Carvalho, Ana Carolina de [UNIFESP] Diagnostic markers Fine-needle aspiration biopsies Head and neck cancers MicroRNAs miR-200 family miR-203 miR-205 Neck metastases |
title_short |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
title_full |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
title_fullStr |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
title_full_unstemmed |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
title_sort |
Accuracy of microRNAs as markers for the detection of neck lymph node metastases in patients with head and neck squamous cell carcinoma |
author |
Carvalho, Ana Carolina de [UNIFESP] |
author_facet |
Carvalho, Ana Carolina de [UNIFESP] Scapulatempo-Neto, Cristovam Maia, Danielle Calheiros Campelo [UNIFESP] Evangelista, Adriane Feijo Morini, Mariana Andozia Carvalho, Andre Lopes Vettore, Andre Luiz [UNIFESP] |
author_role |
author |
author2 |
Scapulatempo-Neto, Cristovam Maia, Danielle Calheiros Campelo [UNIFESP] Evangelista, Adriane Feijo Morini, Mariana Andozia Carvalho, Andre Lopes Vettore, Andre Luiz [UNIFESP] |
author2_role |
author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade Federal de São Paulo (UNIFESP) Barretos Canc Hosp Duke NUS Grad Med Sch |
dc.contributor.author.fl_str_mv |
Carvalho, Ana Carolina de [UNIFESP] Scapulatempo-Neto, Cristovam Maia, Danielle Calheiros Campelo [UNIFESP] Evangelista, Adriane Feijo Morini, Mariana Andozia Carvalho, Andre Lopes Vettore, Andre Luiz [UNIFESP] |
dc.subject.eng.fl_str_mv |
Diagnostic markers Fine-needle aspiration biopsies Head and neck cancers MicroRNAs miR-200 family miR-203 miR-205 Neck metastases |
topic |
Diagnostic markers Fine-needle aspiration biopsies Head and neck cancers MicroRNAs miR-200 family miR-203 miR-205 Neck metastases |
description |
Background: the presence of metastatic disease in cervical lymph nodes of head and neck squamous cell carcinoma (HNSCC) patients is a very important determinant in therapy choice and prognosis, with great impact in overall survival. Frequently, routine lymph node staging cannot detect occult metastases and the post-surgical histologic evaluation of resected lymph nodes is not sensitive in detecting small metastatic deposits. Molecular markers based on tissue-specific microRNA expression are alternative accurate diagnostic markers. Herein, we evaluated the feasibility of using the expression of microRNAs to detect metastatic cells in formalin-fixed paraffin-embedded (FFPE) lymph nodes and in fine-needle aspiration (FNA) biopsies of HNSCC patients.Methods: An initial screening compared the expression of 667 microRNAs in a discovery set comprised by metastatic and non-metastatic lymph nodes from HNSCC patients. the most differentially expressed microRNAs were validated by qRT-PCR in two independent cohorts: i) 48 FFPE lymph node samples, and ii) 113 FNA lymph node biopsies. the accuracy of the markers in identifying metastatic samples was assessed through the analysis of sensitivity, specificity, accuracy, negative predictive value, positive predictive value, and area under the curve values.Results: Seven microRNAs highly expressed in metastatic lymph nodes from the discovery set were validated in FFPE lymph node samples. MiR-203 and miR-205 identified all metastatic samples, regardless of the size of the metastatic deposit. Additionally, these markers also showed high accuracy when FNA samples were examined.Conclusions: the high accuracy of miR-203 and miR-205 warrant these microRNAs as diagnostic markers of neck metastases in HNSCC. These can be evaluated in entire lymph nodes and in FNA biopsies collected at different time-points such as pre-treatment samples, intraoperative sentinel node biopsy, and during patient follow-up. These markers can be useful in a clinical setting in the management of HNSCC patients from initial disease staging and therapy planning to patient surveillance. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-05-09 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:40:30Z |
dc.date.available.fl_str_mv |
2016-01-24T14:40:30Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Bmc Medicine. London: Biomed Central Ltd, v. 13, 14 p., 2015. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/39097 http://dx.doi.org/10.1186/s12916-015-0350-3 |
dc.identifier.issn.none.fl_str_mv |
1741-7015 |
dc.identifier.file.none.fl_str_mv |
WOS000354935300001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/s12916-015-0350-3 |
dc.identifier.wos.none.fl_str_mv |
WOS:000354935300001 |
identifier_str_mv |
Bmc Medicine. London: Biomed Central Ltd, v. 13, 14 p., 2015. 1741-7015 WOS000354935300001.pdf 10.1186/s12916-015-0350-3 WOS:000354935300001 |
url |
http://repositorio.unifesp.br/handle/11600/39097 http://dx.doi.org/10.1186/s12916-015-0350-3 |
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eng |
language |
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Bmc Medicine |
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14 |
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Biomed Central Ltd |
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Biomed Central Ltd |
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