Kuo I-Chun, Kao Huang-Kai, Huang Yenlin, Wang Chun-I, Yi Jui-Shan, Liang Ying, Liao Chun-Ta, Yen Tzu-Chen, Wu Chih-Ching, Chang Kai-Ping
Department of Otolaryngology - Head & Neck Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan.
Department of Plastic & Reconstructive Surgery, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan, Taiwan.
Oncotarget. 2017 Jun 27;8(37):61698-61708. doi: 10.18632/oncotarget.18680. eCollection 2017 Sep 22.
Oral cavity squamous cell carcinoma (OSCC) is a leading cause of cancer-related deaths worldwide and associated with poor prognosis and mortality. Discovery of proteins that can improve OSCC treatment is needed. Using comparative proteome profiling of primary cells derived from OSCC and adjacent noncancerous epithelium, endoplasmic reticulum aminopeptidases 2 (ERAP2) has been identified as an OSCC-associated protein. Compared with the adjacent normal tissues, ERAP2 levels were determined to be significantly elevated in OSCC tissues using quantitative real-time PCR and immunohistochemistry. Importantly, overexpression of ERAP2 was associated with positive N stage, advanced overall stage, positive perineural invasion, and tumor depth ( = 0.041, 0.015, 0.010, and 0.032, respectively). The overall survival rates of patients without and with the ERAP2 overexpression were 71.9% and 56.0%, respectively ( = 0.029). Furthermore, knockdown of ERAP2 inhibited the migration and invasion abilities of OSCC cells. Our results collectively show that ERAP2 overexpression is associated with the cervical metastasis and poorer prognosis of OSCC.
口腔鳞状细胞癌（OSCC）是全球癌症相关死亡的主要原因，且预后和死亡率较差。因此，需要发现能够改善OSCC治疗的蛋白质。通过对源自OSCC和相邻非癌上皮的原代细胞进行比较蛋白质组分析，内质网氨肽酶2（ERAP2）已被确定为一种与OSCC相关的蛋白质。使用定量实时PCR和免疫组织化学方法测定，与相邻正常组织相比，OSCC组织中ERAP2水平显著升高。重要的是，ERAP2的过表达与N分期阳性、总体分期晚期、神经周围浸润阳性和肿瘤深度相关（分别为P = 0.041、0.015、0.010和0.032）。ERAP2未过表达和过表达患者的总生存率分别为71.9%和56.0%（P = 0.029）。此外，敲低ERAP2可抑制OSCC细胞的迁移和侵袭能力。我们的结果共同表明，ERAP2过表达与OSCC的颈部转移和较差预后相关。
