Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma
Decreased prostasin expression is associated with aggressiveness of oral squamous cell carcinoma
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DOI：
10.1007/s13577-021-00575-3
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发表时间：
2021-07
期刊：
影响因子：
4.3
通讯作者：
Koji Yamamoto;Fumiki Yamashita;M. Kawaguchi;Aya Izumi;Takumi Kiwaki;Hiroaki Kataoka;T. Kaneuji;Y. Yamashita;T. Fukushima
中科院分区：
文献类型：
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作者：
Koji Yamamoto;Fumiki Yamashita;M. Kawaguchi;Aya Izumi;Takumi Kiwaki;Hiroaki Kataoka;T. Kaneuji;Y. Yamashita;T. Fukushima
前列腺素是一种糖基磷脂酰肌醇锚定的丝氨酸蛋白酶，广泛表达于上皮细胞中，具有重要的表皮屏障功能。有证据表明前列腺素可能在多种癌症中充当肿瘤抑制因子，但其在口腔鳞状细胞癌 (OSCC) 中的作用仍不清楚。因此，在此，我们对 119 例切除的 OSCC 病例进行了免疫组织化学前列腺素研究。 63% (75/119) 的病例前列腺素表达下降。前列腺素免疫反应性降低（低前列腺素病例）的口腔鳞癌往往表现出较高的组织学分级（p= 0.0088）和更具浸润性的癌细胞形态（p= 0.0024）。然后我们探讨了前列腺素在 OSCC 细胞系 SAS 和 HSC-4 中的作用。 SAS 不表达可检测到的前列腺素水平，而 HSC-4 表达较低但不同的水平。前列腺素过度表达抑制了两种 OSCC 系的体外增殖和迁移。相反，前列腺素沉默显着提高了 HSC-4 的生长速度。最后，我们分析了前列腺素表达对OSCC患者预后的影响；表达减少往往与切除后较短的总生存期相关（p= 0.0291）。我们使用头颈鳞状细胞癌公共数据库（Kaplan-Meier 绘图仪）进行的分析支持了这一趋势。总之，我们发现前列腺素表达降低与 OSCC 的侵袭性特征和较差的预后相关。
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.