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

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da Costa, Bruno Cesar ; Dourado, Mauricio Rocha ; de Moraes, Everton Freitas ; Panini, Luana Mari ; Elseragy, Amr ; Teo, Fabio Haach ; Guimaraes, Gustavo Narvaes ; Machado, Renato Assis ; Risteli, Maija ; Gurgel Rocha, Clarissa Araujo ; Ribeiro Paranaiba, Livia Maris ; Gonzalez-Arriagada, Wilfredo Alejandro ; da Silva, Sabrina Daniela ; Carrinho Ayroza Rangel, Ana Lucia ; Marques, Marcelo Rocha ; Salo, Tuula ; Coletta, Ricardo D.

• Document type: Journal article
• Source: JOURNAL OF ORAL PATHOLOGY & MEDICINE; v. 52, n. 7, p. 9-pg., 2023-05-29.

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. (AU)

• FAPESP's process: 21/08943-8 - Impact of the stress-induced phosphoprotein 1 (STIP1) expression in oral squamous cell carcinoma
• Grantee: Bruno Cesar da Costa
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/01123-8 - Impact of SERPINH1 (serpin family H member 1) knockdown on oral squamous cell carcinoma cells response to cisplatin
• Grantee: Luana Marí Panini
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/13595-9 - Impact of the combination of the histopathological grading system with tumor budding, tumor-stroma ratio and tumor-infiltrating lymphocytes in the prognosis of early-stage oral squamous cell carcinomas.
• Grantee: Gabriela Vivili Domingues Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 22/00994-5 - Analysis of Kaempferol effects in suppression of epithelial-mesenchymal transition-induced chemoresistance in Oral Squamous Cell Carcinoma
• Grantee: Everton Freitas de Morais
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/16077-6 - The prognostic value and biological role of overexpressed proteins in oral squamous cell carcinoma identified by mass spectrometry-based proteomic
• Grantee: Ricardo Della Coletta
• Support Opportunities: Regular Research Grants