Liu Pei-Feng, Chen Chun-Feng, Shu Chih-Wen, Chang Hui-Min, Lee Cheng-Hsin, Liou Huei-Han, Ger Luo-Ping, Chen Chun-Lin, Kang Bor-Hwang
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.
Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
Diagnostics (Basel). 2020 Sep 4;10(9):674. doi: 10.3390/diagnostics10090674.
Ubiquitin-conjugating enzyme 2C (UBE2C) involves in numerous cellular processes and the tumor progression in many cancers. However, its role in oral squamous cell carcinoma (OSCC) is unclear. We aimed to investigate the role and clinical significance of UBE2C in OSCC. The expression levels of UBE2C were examined by immunohistochemistry in 185 buccal mucosa squamous cell carcinomas, 247 tongue squamous cell carcinomas (TSCCs) and 75 lip squamous cell carcinomas. The roles of UBE2C in cell growth, invasion/migration and cancer stemness were also examined in OSCC cells. The expression levels of UBE2C protein were higher in tumor tissues than they were in the corresponding tumor adjacent normal tissues from OSCC patients. Higher UBE2C expression was associated with poor cell differentiation and lymph node invasion in OSCC patients. High UBE2C expression was also correlated with shorter disease-specific survival in TSCC patients having poor cell differentiation, advanced pathological stages, lymph node metastasis as well as receiving radiation therapy. Compared to control cells, OSCC cells in which UBE2C was silenced showed decreased cell proliferation, migration/invasion and colony formation and they exhibited lower expression levels of the following cancer stemness markers-ALDH1/A2, CD44, CD166 and EpCAM. High co-expression levels of UBE2C/CD44, UBE2C/CD166 and UBE2C/EpCAM were associated with poor prognosis in oral cancer patients from The Cancer Genome Atlas database. Our findings indicated that UBE2C might be a potential biomarker for tumorigenesis and prognosis in TSCC.
泛素结合酶2C(UBE2C)参与众多细胞过程以及多种癌症的肿瘤进展。然而,其在口腔鳞状细胞癌(OSCC)中的作用尚不清楚。我们旨在研究UBE2C在OSCC中的作用及临床意义。通过免疫组织化学检测了185例颊黏膜鳞状细胞癌、247例舌鳞状细胞癌(TSCC)和75例唇鳞状细胞癌中UBE2C的表达水平。还在OSCC细胞中检测了UBE2C在细胞生长、侵袭/迁移和癌症干性方面的作用。OSCC患者肿瘤组织中UBE2C蛋白的表达水平高于相应肿瘤旁正常组织。UBE2C高表达与OSCC患者细胞分化差和淋巴结侵袭相关。在细胞分化差、病理分期晚、有淋巴结转移以及接受放射治疗的TSCC患者中,UBE2C高表达也与疾病特异性生存期缩短相关。与对照细胞相比,UBE2C沉默的OSCC细胞显示细胞增殖、迁移/侵袭和集落形成减少,并且它们表现出以下癌症干性标志物——醛脱氢酶1/A2(ALDH1/A2)、CD44、CD166和上皮细胞黏附分子(EpCAM)的较低表达水平。来自癌症基因组图谱数据库的口腔癌患者中,UBE2C/CD44、UBE2C/CD166和UBE2C/EpCAM的高共表达水平与预后不良相关。我们的研究结果表明,UBE2C可能是TSCC肿瘤发生和预后的潜在生物标志物。