Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma

PLoS One. 2016 Mar 31;11(3):e0152165. doi: 10.1371/journal.pone.0152165. eCollection 2016.

Abstract

Background: 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.

Methodology/principal findings: Tissue 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.

Conclusions: We 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Cathepsin B / analysis*
  • Cathepsin B / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Disease Progression
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphatic Metastasis / diagnosis
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • Male
  • Middle Aged
  • Mouth / pathology*
  • Mouth Neoplasms / diagnosis
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Prognosis
  • RNA Interference
  • RNA, Small Interfering / genetics

Substances

  • RNA, Small Interfering
  • Cathepsin B

Grants and funding

This study was supported by a research grant from National Science Council, Taiwan (NSC101-2314-B-371-002-MY3). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.