SERPINE2 is an oral cancer-promoting factor that induces angiogenesis and lymphangiogenesis
SERPINE2 is an oral cancer-promoting factor that induces angiogenesis and lymphangiogenesis
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DOI：
10.1007/s10147-021-01970-4
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发表时间：
2021-06-25
影响因子：
3.3
通讯作者：
Kirita, Tadaaki
中科院分区：
文献类型：
--
作者：
Sasahira, Tomonori;Kurihara-Shimomura, Miyako;Kirita, Tadaaki
背景LEM结构域1（LEMD1）是一种新的参与口腔鳞状细胞癌（OSCC）发生发展的因子。我们先前进行了微阵列分析，发现丝氨酸蛋白酶抑制剂肽酶抑制剂，进化枝E，成员2（SERPINE2）是LEMD1相关的信号。SERPINE2是一种具有分泌能力的细胞外丝氨酸蛋白酶抑制剂。尽管SERPINE2在许多癌症中表现出肿瘤促进特性，但一些报告表明SRPINE2也具有肿瘤抑制功能。因此，关于它在癌症中的作用还有许多不清楚的地方。在这项研究中，我们研究了SERPINE2在口腔鳞癌中的表达。方法检测42例口腔鳞状细胞癌冰冻标本中SERPINE2基因的表达和分泌水平，并对167例口腔鳞状细胞癌进行SERPINE2免疫组化染色。此外，使用OSCC细胞和内皮细胞分析SERPINE2对血管生成和淋巴管生成的作用。结果在冰冻标本中，SERPINE2的基因表达（P < 0.0001）和分泌水平（P < 0.0001）在口腔鳞癌中均高于正常口腔粘膜。免疫组化分析显示，SERPINE 2表达与胃癌浸润深度（P = 0.0163）、淋巴结转移（P = 0.0085）、微血管密度（P < 0.0001）和淋巴管密度（P < 0.0001）相关。此外，单因素和多因素分析表明，SERPINE2表达水平是一个独立的口腔鳞癌预后不良的因素。使用OSCC细胞的体外研究显示SERPINE2促进血管生成和淋巴管生成。结论SRPX 2可能是口腔鳞癌的一个有用的肿瘤标志物。
Background LEM domain containing 1 (LEMD1) is a novel factor involved in the development of oral squamous cell carcinoma (OSCC). We previously performed a microarray analysis and found that serpin peptidase inhibitor, clade E, member 2 (SERPINE2) is an LEMD1-related signal. SERPINE2 is an extracellular serine proteinase inhibitor with secretory capacity. Although SERPINE2 displays tumor-promoting properties in many cancers, some reports indicate that SRPINE2 also has a tumor-suppressing function. Therefore, there are many unclear points about its role in cancer. In this study, we investigated SERPINE2 expression in OSCC. Methods The gene expression and secretion levels of SERPINE2 were examined in 42 frozen specimens of OSCC, and SERPINE2 immunostaining was investigated in 167 cases of OSCC. Furthermore, the effect of SERPINE2 on angiogenesis and lymphangiogenesis was analyzed using OSCC cells and endothelial cells. Results In the frozen specimens, the gene expression (P < 0.0001) and secretion levels (P < 0.0001) of SERPINE2 were higher in OSCC than in the normal oral mucosa. According to the immunohistochemical analysis, SERPINE2 expression was correlated with the depth of invasion (P = 0.0163), nodal metastasis (P = 0.0085), microvessel density (P < 0.0001), and lymphovessel density (P < 0.0001). Additionally, univariate and multivariate analyses indicated that the SERPINE2 expression level was an independent poor prognostic factor for OSCC. In vitro studies using OSCC cells revealed that SERPINE2 promotes angiogenesis and lymphangiogenesis. Conclusion These results suggest that SRPX2 might be a useful tumor marker for OSCC.