title: Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients.
abstract: BACKGROUND
  Several studies have found that Cathepsin B (CTSB) is up-regulated in many tumor types and facilitates tumor progression. However, the role of CTSB in hepatocellular carcinoma (HCC) progression remains unclear. This study was aimed at investigating the expression and role of CTSB in HCC in a large set of samples and cell lines (MHCC-97H and MHCC-97 L), and evaluating the clinical and prognostic significance of CTSB protein in patients with HCC.
  
  
  METHODS
  The expression of CTSB was examined in HCC tissue and cell lines by Western-blotting, Real-time PCR, and immunohistochemical staining. Wound healing assay and invasion assay were used to verify the effect of CTSB on the migration and invasion ability of HCC cell lines. Tumor formation assay in nude mice was used to analyze the effect of CTSB on the tumorigenicity of HCC cell lines.
  
  
  RESULTS
  The status of CTSB protein in carcinoma tissues is much higher than that in paracarcinoma tissues. The overall survival of the patients with high CTSB expression was significantly shorter than the low CTSB expression group. High CTSB expression was significantly correlated with advanced clinical staging, histological grade, and tumor recurrence. In vitro and in vivo experiments demonstrated that over-expression of CTSB in MHCC-97 L cells promoted cell invasion and tumor progression ability. Down-regulation of CTSB in MHCC-97H showed the opposite effects. These phenotypic changes caused by CTSB knockdown or over-expression correlated with expression of the matrix metallopeptidase MMP-9. Moreover, multivariate analysis suggested that CTSB expression might be an independent prognostic indicator for the survival of HCC patients after curative surgery.
  
  
  CONCLUSIONS
  CTSB might be involved in the development and progression of HCC as an oncogene, and thereby may be a valuable prognostic marker for HCC patients.
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China. software23@163.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Ruan
authors.affiliation: The Institute of Gynecology and Obstetrics, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510315, Guangdong Province, People's Republic of China. ceozhy_1985@126.com.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Sun Yat-Sen University, Guangzhou, 510000, Guangdong Province, People's Republic of China. 656803493@qq.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Rong
authors.affiliation: Department of pharmacy, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510000, Guangdong Province, People's Republic of China. 284041226@qq.com.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Rong
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China. zhaojia233@163.com.
authors.forename: Junyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, People's Republic of China. duyan233@163.com.
authors.forename: Weijia
authors.initials: W
authors.lastname: Fang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, Zhejiang Province, People's Republic of China. Haozhao@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangzhou, 510515, Guangdong Province, People's Republic of China. luorc0001@126.com.
authors.forename: Rongcheng
authors.initials: R
authors.lastname: Luo
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology*; D002401:Cathepsin B / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D002401:Cathepsin B; D020780:Matrix Metalloproteinase 9