Abstract

BackgroundCathepsin B (CTSB), a member of the cathepsin family, is a cysteine protease that is widely distributed in the lysosomes of cells in various tissues. It is overexpressed in several human cancers and may be related to tumorigenesis. The main purpose of this study was to analyze CTSB expression in oral squamous cell carcinoma (OSCC) and its correlation with patient prognosis.Methodology/Principal FindingsTissue microarrays were used to detect CTSB expression in 280 patients and to examine the association between CTSB expression and clinicopathological parameters. In addition, the metastatic effects of the CTSB knockdown on two oral cancer cell lines were investigated by transwell migration assay. Cytoplasmic CTSB expression was detected in 34.6% (97/280) of patients. CTSB expression was correlated with positive lymph node metastasis (p = 0.007) and higher tumor grade (p = 0.008) but not with tumor size and distant metastasis. In addition, multivariate analysis using a Cox proportional hazards model revealed a higher hazard ratio, demonstrating that CTSB expression was an independent unfavorable prognostic factor in buccal mucosa carcinoma patients. Furthermore, the Kaplan–Meier curve revealed that buccal mucosa OSCC patients with positive CTSB expression had significantly shorter overall survival. Moreover, treatment with the CTSB siRNA exerted an inhibitory effect on migration in OC2 and CAL27 oral cancer cells.ConclusionsWe conclude that CTSB expression may be useful for determining OSCC prognosis, particularly for patients with lymph node metastasis, and may function as a biomarker of the survival of OSCC patients in Taiwan.

Highlights

  • Oral cancer is the sixth most common cancer worldwide, and approximately 90% of oral cancers are oral squamous cell carcinoma (OSCC) [1]

  • We conclude that Cathepsin B (CTSB) expression may be useful for determining OSCC prognosis, for patients with lymph node metastasis, and may function as a biomarker of the survival of OSCC patients in Taiwan

  • Since we found that expression of CTSB was significantly correlated with the presence of lymph node metastasis, the effects of the CTSB knockdown on the oral cancer cell line were investigated by cell transwell migration assay

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Summary

Introduction

Oral cancer is the sixth most common cancer worldwide, and approximately 90% of oral cancers are oral squamous cell carcinoma (OSCC) [1]. Common treatments for oral cancer include surgery, radiotherapy, or chemotherapy. Cathepsin B (CTSB), a member of the cathepsin family, is a cysteine protease that is widely distributed in the lysosomes of cells in various tissues. It is overexpressed in several human cancers and may be related to tumorigenesis. The main purpose of this study was to analyze CTSB expression in oral squamous cell carcinoma (OSCC) and its correlation with patient prognosis

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