ROCK1 as a novel prognostic marker in vulvar cancer
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1471-2407-14-822 http://hdl.handle.net/11449/117314 |
Resumo: | Background: Vulvar carcinoma is an infrequent tumour, accounting for fewer than 3% of all malignant tumours that affect women, but its incidence is rising in the past few decades. In young women, the manifestation of the vulvar carcinoma is often linked to risk factors such as smoking and HPV infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC).Methods: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm the involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH).Results: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal tissue compared with the tumour samples (p = 0.016). By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour areas were positive for ROCK1. Greater expression of ROCK1 was associated with the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p = 0.002). In addition, higher ROCK1 levels correlated with greater recurrence-free survival (p = 0.001). Loss of ROCK1 was independently linked to worse cancer-specific survival (p = 0.0054) by multivariate analysis. This finding was validated by IHC, which demonstrated enhanced protein expression in normal versus tumour tissue (p < 0.001). By aCGH, 42.9% of samples showed a gain in copy number of the ROCK1 gene.Conclusions: ROCK1 is lower expressed in tumour tissue when compared with adjacent normal vulvar epithelia. In an independent sample set of VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and a poor prognosis. These findings provide important information for the clinical management of vulvar cancer. |
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spelling |
ROCK1 as a novel prognostic marker in vulvar cancerVulvar carcinomaROCK1qRT-PCRImmunohistochemistryaCGHPrognosisBackground: Vulvar carcinoma is an infrequent tumour, accounting for fewer than 3% of all malignant tumours that affect women, but its incidence is rising in the past few decades. In young women, the manifestation of the vulvar carcinoma is often linked to risk factors such as smoking and HPV infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC).Methods: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm the involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH).Results: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal tissue compared with the tumour samples (p = 0.016). By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour areas were positive for ROCK1. Greater expression of ROCK1 was associated with the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p = 0.002). In addition, higher ROCK1 levels correlated with greater recurrence-free survival (p = 0.001). Loss of ROCK1 was independently linked to worse cancer-specific survival (p = 0.0054) by multivariate analysis. This finding was validated by IHC, which demonstrated enhanced protein expression in normal versus tumour tissue (p < 0.001). By aCGH, 42.9% of samples showed a gain in copy number of the ROCK1 gene.Conclusions: ROCK1 is lower expressed in tumour tissue when compared with adjacent normal vulvar epithelia. In an independent sample set of VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and a poor prognosis. These findings provide important information for the clinical management of vulvar cancer.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)AC Camargo Canc Ctr, Mol Morphol Lab, Sao Paulo, BrazilUniv Sao Paulo, Sch Med, Dept Obstet & Gynecol, Sao Paulo, BrazilFleury Inst, Dept Pathol, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Gynecol Oncol, Sao Paulo, BrazilAC Camargo Canc Ctr, Dept Anat Pathol, Sao Paulo, BrazilAC Camargo Canc Ctr, NeoGene Lab, Sao Paulo, BrazilUNESP, Fac Med, Dept Urol, Botucatu, SP, BrazilUNESP, Fac Med, Dept Urol, Botucatu, SP, BrazilBiomed Central LtdAC Camargo Canc CtrUniversidade de São Paulo (USP)Fleury InstUniversidade Estadual Paulista (Unesp)Akagi, Erica M.Lavorato-Rocha, Andre M.Maia, Beatriz de MeloRodrigues, Iara S.Carvalho, Katia C.Stiepcich, Monica M.Baiocchi, GlaucoSato-Kuwabara, YukieRogatto, Silvia Regina [UNESP]Soares, Fernando A.Rocha, Rafael M.2015-03-18T15:55:48Z2015-03-18T15:55:48Z2014-11-07info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://dx.doi.org/10.1186/1471-2407-14-822Bmc Cancer. London: Biomed Central Ltd, v. 14, 10 p., 2014.1471-2407http://hdl.handle.net/11449/11731410.1186/1471-2407-14-822WOS:000345161300001WOS000345161300001.pdf2259986546265579Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengBmc Cancer3.2881,464info:eu-repo/semantics/openAccess2024-01-18T06:33:38Zoai:repositorio.unesp.br:11449/117314Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-18T06:33:38Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
ROCK1 as a novel prognostic marker in vulvar cancer |
title |
ROCK1 as a novel prognostic marker in vulvar cancer |
spellingShingle |
ROCK1 as a novel prognostic marker in vulvar cancer Akagi, Erica M. Vulvar carcinoma ROCK1 qRT-PCR Immunohistochemistry aCGH Prognosis |
title_short |
ROCK1 as a novel prognostic marker in vulvar cancer |
title_full |
ROCK1 as a novel prognostic marker in vulvar cancer |
title_fullStr |
ROCK1 as a novel prognostic marker in vulvar cancer |
title_full_unstemmed |
ROCK1 as a novel prognostic marker in vulvar cancer |
title_sort |
ROCK1 as a novel prognostic marker in vulvar cancer |
author |
Akagi, Erica M. |
author_facet |
Akagi, Erica M. Lavorato-Rocha, Andre M. Maia, Beatriz de Melo Rodrigues, Iara S. Carvalho, Katia C. Stiepcich, Monica M. Baiocchi, Glauco Sato-Kuwabara, Yukie Rogatto, Silvia Regina [UNESP] Soares, Fernando A. Rocha, Rafael M. |
author_role |
author |
author2 |
Lavorato-Rocha, Andre M. Maia, Beatriz de Melo Rodrigues, Iara S. Carvalho, Katia C. Stiepcich, Monica M. Baiocchi, Glauco Sato-Kuwabara, Yukie Rogatto, Silvia Regina [UNESP] Soares, Fernando A. Rocha, Rafael M. |
author2_role |
author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
AC Camargo Canc Ctr Universidade de São Paulo (USP) Fleury Inst Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Akagi, Erica M. Lavorato-Rocha, Andre M. Maia, Beatriz de Melo Rodrigues, Iara S. Carvalho, Katia C. Stiepcich, Monica M. Baiocchi, Glauco Sato-Kuwabara, Yukie Rogatto, Silvia Regina [UNESP] Soares, Fernando A. Rocha, Rafael M. |
dc.subject.por.fl_str_mv |
Vulvar carcinoma ROCK1 qRT-PCR Immunohistochemistry aCGH Prognosis |
topic |
Vulvar carcinoma ROCK1 qRT-PCR Immunohistochemistry aCGH Prognosis |
description |
Background: Vulvar carcinoma is an infrequent tumour, accounting for fewer than 3% of all malignant tumours that affect women, but its incidence is rising in the past few decades. In young women, the manifestation of the vulvar carcinoma is often linked to risk factors such as smoking and HPV infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC).Methods: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm the involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH).Results: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal tissue compared with the tumour samples (p = 0.016). By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour areas were positive for ROCK1. Greater expression of ROCK1 was associated with the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p = 0.002). In addition, higher ROCK1 levels correlated with greater recurrence-free survival (p = 0.001). Loss of ROCK1 was independently linked to worse cancer-specific survival (p = 0.0054) by multivariate analysis. This finding was validated by IHC, which demonstrated enhanced protein expression in normal versus tumour tissue (p < 0.001). By aCGH, 42.9% of samples showed a gain in copy number of the ROCK1 gene.Conclusions: ROCK1 is lower expressed in tumour tissue when compared with adjacent normal vulvar epithelia. In an independent sample set of VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and a poor prognosis. These findings provide important information for the clinical management of vulvar cancer. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-11-07 2015-03-18T15:55:48Z 2015-03-18T15:55:48Z |
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.uri.fl_str_mv |
http://dx.doi.org/10.1186/1471-2407-14-822 Bmc Cancer. London: Biomed Central Ltd, v. 14, 10 p., 2014. 1471-2407 http://hdl.handle.net/11449/117314 10.1186/1471-2407-14-822 WOS:000345161300001 WOS000345161300001.pdf 2259986546265579 |
url |
http://dx.doi.org/10.1186/1471-2407-14-822 http://hdl.handle.net/11449/117314 |
identifier_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 14, 10 p., 2014. 1471-2407 10.1186/1471-2407-14-822 WOS:000345161300001 WOS000345161300001.pdf 2259986546265579 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bmc Cancer 3.288 1,464 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
10 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
publisher.none.fl_str_mv |
Biomed Central Ltd |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1803047369684549632 |