4.2 Article

Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma

Journal

HUMAN CELL
Volume 34, Issue 5, Pages 1434-1445

Publisher

SPRINGER JAPAN KK
DOI: 10.1007/s13577-021-00575-3

Keywords

Oral squamous cell carcinoma; Head and neck squamous cell carcinoma; Prostasin; Epithelial-mesenchymal transition; Prognosis

Categories

Funding

  1. Japan Society for the Promotion of Science [KAKENHI 20K18483, 17K08764]
  2. Miyazaki University Hospital
  3. Grants-in-Aid for Scientific Research [17K08764] Funding Source: KAKEN

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The study revealed that decreased expression of prostasin in oral squamous cell carcinoma is associated with more aggressive features and a poorer prognosis. Additionally, prostasin overexpression suppressed the proliferation and migration of OSCC cell lines in vitro, suggesting a potential role in tumor suppression.
Prostasin is a glycosylphosphatidylinositol-anchored serine protease widely expressed in epithelial cells, with crucial epidermal barrier functions. Evidence has suggested prostasin may have served as a tumor suppressor in various cancers, but its role in oral squamous cell carcinoma (OSCC) remains unclear. Thus, herein, we conducted an immunohistochemical prostasin study in 119 resected OSCC cases. Prostasin expression was decreased in 63% (75/119) of cases. OSCC with decreased prostasin immunoreactivity (low prostasin cases) tended to show a higher histological grade (p = 0.0088) and a more infiltrative cancer cell morphology (p = 0.0024). We then explored the role of prostasin in the OSCC cell lines: SAS and HSC-4. SAS did not express detectable prostasin levels, whereas HSC-4 expressed low but distinct levels. Prostasin overexpression suppressed the proliferation and migration of both OSCC lines in vitro. Conversely, prostasin silencing significantly enhanced growth rates of HSC-4. Finally, we analyzed the impact of prostasin expression on the prognosis of patients with OSCC; decreased expression tended to correlate with shorter overall survival (p = 0.0291) after resection. This trend was supported by our analyses using a public database (Kaplan-Meier plotter) of head and neck squamous cell carcinomas. In conclusion, we showed decreased prostasin expression was associated with aggressive features and a poorer prognosis of OSCC.

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