Overexpression of heat-shock protein 47 impacts survival of patients with oral squamous cell carcinoma
da Costa, Bruno Cesar; Dourado, Mauricio Rocha; de Moraes, Everton Freitas; Panini, Luana Marí; Elseragy, Amr; Téo, Fábio Haach; Guimarães, Gustavo Narvaes; Machado, Renato Assis; Risteli, Maija; Gurgel Rocha, Clarissa Araujo; Paranaíba, Lívia Máris Ribeiro; González-Arriagada, Wilfredo Alejandro; da Silva, Sabrina Daniela; Rangel, Ana Lucia Carrinho Ayroza; Marques, Marcelo Rocha; Salo, Tuula; Coletta, Ricardo D. (2023-05-29)
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
© 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.
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https://urn.fi/URN:NBN:fi-fe2023070480357
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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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