Abstract
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.
Highlights
More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) which is typically observed on the tongue, buccal mucosa and lips [1]
We first indicated that (1) the expression level of Ubiquitin-conjugating enzyme 2C (UBE2C) was higher in tumor tissues of OSCC patients than it was in CTAN tissues; (2) the high expression level of UBE2C in tumor tissues was associated with poor cell differentiation and lymph node invasion in OSCC patients, especially in BMSCC and tongue squamous cell carcinomas (TSCCs)
Patients; (3) the high expression level of UBE2C in tumor tissues was associated with shorter disease-specific survival (DSS) in TSCC patients with poor cell differentiation, advanced pathological stage, lymph node metastasis and postoperative radiation therapy; (4) UBE2C was involved in cell proliferation, migration, invasion, colony formation and cancer stemness of OSCC cells; and (5) the high co-expression levels of UBE2C and cancer stemness markers such as CD44, CD166 and EpCAM were associated with poor prognosis in oral cancer patients including TSCC patients from The Cancer Genome Atlas (TCGA) database
Summary
More than 90% of oral cancers are oral squamous cell carcinoma (OSCC) which is typically observed on the tongue, buccal mucosa and lips [1]. Alcohol drinking, betel quid chewing, chronic periodontitis [2] and viral infections [3] are major risk factors contributing to the incidence of OSCC. OSCC is a highly aggressive cancer with frequent local recurrences and lymph node metastases [4]. The overall 5-year survival rate for OSCC patients have not been improved and remained at approximately 50% for several decades [5]. How a diagnostic/prognostic assessment of gene expression could be translated into better patient survival. The aim of biomarker tests is probably to identify/stratify patients for certain therapeutic intervention. Identifying reliable diagnostic and prognostic biomarkers for OSCC is urgent
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