title: PRSS8 is Downregulated and Suppresses Tumour Growth and Metastases in Hepatocellular Carcinoma.
abstract: BACKGROUND
  Protease serine 8 (PRSS8), a trypsin-like serine peptidase, has been shown to function as a tumour suppressor in various malignancies. The present study aimed to investigate the expression pattern, prognostic value and the biological role of PRSS8 in human hepatocellular carcinoma (HCC).
  
  
  METHODS
  PRSS8 expression in 106 HCC surgical specimens was examined by Real-time polymerase chain reaction (PCR) and immunohistochemistry, and its clinical significance was analysed. The role of PRSS8 in cell proliferation, apoptosis and invasion were examined in vitro and in vivo.
  
  
  RESULTS
  PRSS8 mRNA and protein expression were decreased in most HCC tumours from that in matched adjacent non-tumour tissues. Low intratumoral PRSS8 expression was significantly correlated with poor overall survival (OS) in patients with HCC (P = 0.001). PRSS8 expression was an independent prognostic factor for OS (hazard ratio [HR] = 1.704, P = 0.009). Furthermore, restoring PRSS8 expression in high metastatic HCCLM3 cells significantly inhibited cell proliferation and invasion. In contrast, silencing PRSS8 expression in non-metastatic HepG2 cells significantly enhanced cell growth and invasion. Moreover, our in vivo data revealed that attenuated PRSS8 expression in HepG2 cells greatly promoted tumour growth, while overexpression of PRSS8 remarkably inhibited tumour growth in an HCCLM3 xenograft model. Enhanced cell growth and invasion ability mediated by the loss of PRSS8 expression was associated with downregulation of PTEN, Bax and E-cadherin and an upregulation in Bcl-2, MMP9 and N-cadherin.
  
  
  CONCLUSIONS
  Our data demonstrate that PRSS8 may serve as a tumour suppressor in HCC progression, and represent a valuable prognostic marker and potential therapeutic target for HCC.
authors.affiliation: Department of Gastroenterol/ogy and Hepatology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Guozhan
authors.initials: G
authors.lastname: Jia
authors.forename: Binya
authors.initials: B
authors.lastname: Shi
authors.forename: Guanqun
authors.initials: G
authors.lastname: Ge
authors.forename: Hongbin
authors.initials: H
authors.lastname: Duan
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays; D000099271:Prostasin
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D019253:Proto-Oncogene Proteins c-bcl-2; D012697:Serine Endopeptidases; D000099271:Prostasin; C513384:CDH1 protein, human