Yang Wei-En, Ho Chuan-Chen, Yang Shun-Fa, Lin Shu-Hui, Yeh Kun-Tu, Lin Chiao-Wen, Chen Mu-Kuan
Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan.
PLoS One. 2016 Mar 31;11(3):e0152165. doi: 10.1371/journal.pone.0152165. eCollection 2016.
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.
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.
组织蛋白酶B（CTSB）是组织蛋白酶家族的成员，是一种半胱氨酸蛋白酶，广泛分布于各种组织细胞的溶酶体中。它在几种人类癌症中过表达，可能与肿瘤发生有关。本研究的主要目的是分析CTSB在口腔鳞状细胞癌（OSCC）中的表达及其与患者预后的相关性。
方法/主要发现：使用组织微阵列检测280例患者的CTSB表达，并检查CTSB表达与临床病理参数之间的关联。此外，通过Transwell迁移试验研究了CTSB敲低对两种口腔癌细胞系的转移作用。34.6%（97/280）的患者检测到细胞质CTSB表达。CTSB表达与阳性淋巴结转移（p = 0.007）和更高的肿瘤分级（p = 0.008）相关，但与肿瘤大小和远处转移无关。此外，使用Cox比例风险模型进行的多变量分析显示风险比更高，表明CTSB表达是颊黏膜癌患者独立的不良预后因素。此外，Kaplan-Meier曲线显示CTSB表达阳性的颊黏膜OSCC患者的总生存期明显较短。此外，用CTSB siRNA处理对OC2和CAL27口腔癌细胞的迁移具有抑制作用。
我们得出结论，CTSB表达可能有助于确定OSCC的预后，特别是对于有淋巴结转移的患者，并且可能作为台湾OSCC患者生存的生物标志物。
