title: Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis.
abstract: OBJECTIVE
  The purpose of this study is to investigate differentially expressed genes using DNA microarray between advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasis and that with a more advanced tumor stage but without LN metastasis.
  
  
  METHODS
  Five sample pairs of gastric cancer tissue and normal gastric mucosa were taken from three patients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNA microarray experiments were analyzed, and candidate genes were identified using a volcano plot that showed ≥ 2-fold differential expression and were significant by Welch's t test (p < 0.05) between highN and lowN. Those selected genes were validated independently by reverse-transcriptase-polymerase chain reaction (RT-PCR) using five AGC patients, and tissue-microarray (TMA) comprising 47 AGC patients.
  
  
  RESULTS
  CFTR, LAMC2, SERPINE2, F2R, MMP7, FN1, TIMP1, plasminogen activator inhibitor-1 (PAI-1), ITGB8, SDS, and TMPRSS4 were commonly up-regulated over 2-fold in highN. REG3A, CD24, ITLN1, and WBP5 were commonly down-regulated over 2-fold in lowN. Among these genes, overexpression of PAI-1 was validated by RT-PCR, and TMA showed 16.7% (7/42) PAI-1 expression in T3N3, but none (0/5) in T4N0 (p=0.393).
  
  
  CONCLUSIONS
  DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Yun-Suhk
authors: YS
authors: Suh
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Jieun
authors: J
authors: Yu
authors: Theragen Bio Institute, TheragenEtex, Suwon, Korea.
authors: Byung Chul
authors: BC
authors: Kim
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Boram
authors: B
authors: Choi
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Tae-Su
authors: TS
authors: Han
authors: Department of Surgery, SMG-SNU Boramae Medical Center, Seoul, Korea.
authors: Hye Seong
authors: HS
authors: Ahn
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Seong-Ho
authors: SH
authors: Kong
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Hyuk-Joon
authors: HJ
authors: Lee
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors: Woo Ho
authors: WH
authors: Kim
authors: Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Han-Kwang
authors: HK
authors: Yang
mesh_terms: D000368:Aged; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D000073718:Pancreatitis-Associated Proteins; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000073718:Pancreatitis-Associated Proteins; D017395:Plasminogen Activator Inhibitor 1; C000612141:REG3A protein, human
keywords: Lymph nodes; Neoplasm metastasis; Oligonucleotide array sequence analysis; Plasminogen activator inhibitor 1; Stomach neoplasms