Abstract
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 (P = 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 (P = 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.
Highlights
Head and neck cancers are the sixth most common malignancy worldwide, and more than 90% are squamous cell carcinomas
With spectral counting-based protein quantification [5], we revealed that expression of endoplasmic reticulum aminopeptidases 2 (ERAP2) was elevated in Oral cavity squamous cell carcinoma (OSCC) cells compared to noncancerous cells
We performed proteome profiling for established primary cells using GeLC-MS/MS and identified that ERAP2 could play a vital role in the metastasis of OSCC tumors, suggesting that proteome analysis of primary oral epithelial cells is a feasible strategy for OSCC biomarker identification, and that ERAP2 is a potentially useful tissue marker for the prognosis of OSCC
Summary
Head and neck cancers are the sixth most common malignancy worldwide, and more than 90% are squamous cell carcinomas. Oral cavity squamous cell carcinoma (OSCC) accounts for the vast majority of all head and neck squamous cell carcinomas [1]. Alcohol use, smokeless tobacco products, betel quid, inflammation, and oncogenic viruses are the major risk factors for OSCC [2]. Treatment modalities are mainly based on T staging and include surgery and adjuvant therapy including chemotherapy and radiotherapy. Cervical lymph node www.impactjournals.com/oncotarget Patienta Established Sex Age (years). B cancerous male buccal mucosa C floor of mouth TNM stage
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