title: Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer.
abstract: BACKGROUND
  In a previous study, we reported that serpin peptidase inhibitor clade A member 1 (serpinA1) is upregulated in Snail-overexpressing gastric cancer. Although serpinA1 has been studied in several types of cancer, little is known about its roles and mechanisms of action. In this study, we examined the role of serpinA1 in the migration and invasion of gastric cancers and determined its underlying mechanism.
  
  
  METHODS
  Expression levels were assessed by western blot analyses and real-time PCR. Snail binding to serpinA1 promoter was analysed by chromatin immunoprecipitation (ChIP) assays. The roles of serpinA1 were studied using cell invasion and migration assays. In addition, the clinicopathologic and prognostic significance of serpinA1 expression were validated in 400 gastric cancer patients using immunohistochemical analysis.
  
  
  RESULTS
  Overexpression of Snail resulted in upregulation of serpinA1 in gastric cancer cell lines, AGS and MKN45, whereas knockdown of Snail inhibited serpinA1 expression. Chromatin immunoprecipitation analysis showed that overexpression of Snail increased Snail recruitment to the serpinA1 promoter. Overexpression of serpinA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of serpinA1 decreased invasion and migration. Moreover, serpinA1 increased mRNA levels and release of metalloproteinase-8 in gastric cancer cells. Serpin peptidase inhibitor clade A member 1 was observed in the cytoplasm of tumour cells and the stroma by immunohistochemistry. Enhanced serpinA1 expression was significantly associated with increased tumour size, advanced T stage, perineural invasion, lymphovascular invasion, lymph node metastases, and shorter overall survival.
  
  
  CONCLUSIONS
  Serpin peptidase inhibitor clade A member 1 induces the invasion and migration of gastric cancer cells and its expression is associated with the progression of gastric cancer. These results may provide a potential target to prevent invasion and metastasis in gastric cancer.
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Kwon
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: J R
authors.initials: JR
authors.lastname: Lee
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: H K
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: T Y
authors.initials: TY
authors.lastname: Jeon
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Surgery, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: D H
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: G H
authors.initials: GH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Pusan National University Hospital and Pusan National University School of Medicine, and BioMedical Research Institute, Pusan National University Hospital, 1-10 Ami-Dong, Seo-Gu, Busan 602-739, Korea.
authors.forename: D Y
authors.initials: DY
authors.lastname: Park
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000515:alpha 1-Antitrypsin