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da Costa, BC, Dourado, MR, de Moraes, EF, et al. Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma. J Oral Pathol Med. 2023; 52(7): 601-609. doi:10.1111/jop.13455

Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma

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Author: da Costa, Bruno Cesar1; Dourado, Mauricio Rocha1; de Moraes, Everton Freitas1;
Organizations: 1Department of Oral Diagnosis and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil
2Research Unit of Population Health, University of Oulu, Medical Research Centre and Oulu University Hospital, Oulu, Finland
3Department of Biosciences and Graduate Program in Oral Biology, Piracicaba Dental School, University of Campinas, Piracicaba, Sao Paulo, Brazil
4Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Federal University of Bahia and Dor Institute, Salvador, Bahia, Brazil
5Department of Pathology and Parasitology, Institute of Biomedical Sciences, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil
6Facultad de Odontología and Centro de Investigacion e Innovacion Biomédica (CIIB), Universidad de los Andes, Santiago, Chile
7Lady Davis Institute for Medical Research and Segal Cancer Center, Jewish General Hospital, and Department of Otolaryngology-Head and Neck Surgery, McGill University, Montreal, Quebec, Canada
8Department of Oral Pathology and Oral Medicine, Dental School, Western Paraná State University, Cascavel, Paraná, Brazil
9Department of Oral and Maxillofacial Diseases and Department of Pathology, Helsinki University Central Hospital, and Translational Immunology Research Program, University of Helsinki, Helsinki, Finland
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe2023070480357
Language: English
Published: John Wiley & Sons, 2023
Publish Date: 2024-05-29
Description:

Abstract

Background: The expression of heat-shock protein 47 (HSP47) has been linked to collagen synthesis control and implicated in fibrotic disorders, but more recent studies have demonstrated its role in solid tumors. In this study, we explored the prognostic impact of HSP47 in oral squamous cell carcinomas (OSCC) and determined the in vitro effects of its loss-of-function on viability, proliferation, migration, invasion, and resistance to cisplatin of OSCC cells.

Methods: The HSP47 expression in tumor samples was assessed by immunohistochemistry in two independent cohorts totaling 339 patients with OSCC, and protein levels were associated with clinicopathological features and survival outcomes. The OSCC cell lines HSC3 and SCC9 were transduced with lentivirus expressing short hairpin RNA to stably silence HSP47 and used in assays to measure cellular viability, proliferation, migration, and invasion.

Results: HSP47 was overexpressed in OSCC samples, and its overexpression was significantly and independently associated with poor disease-specific survival and shortened disease-free survival in both OSCC cohorts. The knockdown of HSP47 showed no effects on cell viability or cisplatin sensitivity, but impaired significantly proliferation, migration, and invasion of OSCC cells, with stronger effects on SCC9 cells.

Conclusion: Our results show a significant prognostic impact of HSP47 overexpression in OSCC and reveal that HSP47 inhibition impairs the proliferation, migration, and invasion of OSCC cells. HSP47 may represent a potential therapeutic target for OSCC.

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Series: Journal of oral pathology & medicine
ISSN: 0904-2512
ISSN-E: 1600-0714
ISSN-L: 0904-2512
Volume: 52
Issue: 7
Pages: 601 - 609
DOI: 10.1111/jop.13455
OADOI: https://oadoi.org/10.1111/jop.13455
Type of Publication: A1 Journal article – refereed
Field of Science: 313 Dentistry
3122 Cancers
Subjects:
SERPINH1
invasion
oral cancer
prognosis
proliferation
Article
Funding: This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, 2018/16077-6 to Ricardo D. Coletta), and from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, 407814/2018-3 to Ricardo D. Coletta). Bruno Cesar da Costa (2021/08943-8), Everton Freitas de Moraes (2022/00994-5), Luana Marí Panini (2022/01123-8), and Mauricio Rocha Dourado (2021/13595-9) were research fellows supported by FAPESP. Amr Elsegary, Maija Risteli, and Tuula Salo were funded by Universities of Oulu and Helsinki, the Sigrid Juselius Foundation, and Oulu and Helsinki University Hospital special state support for research. Lívia Máris Ribeiro Paranaíba received a grant from Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, PPM-00179-18).
Copyright information: © 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. This is the peer reviewed version of the following article: da Costa, BC, Dourado, MR, de Moraes, EF, et al. Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma. J Oral Pathol Med. 2023; 52(7): 601-609. doi:10.1111/jop.13455. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.