Overexpression of plasminogen activator inhibitor-1 in advanced gastric cancer with aggressive lymph node metastasis

Yun Suhk Suh, Jieun Yu, Byung Chul Kim, Boram Choi, Tae Su Han, Hye Seong Ahn, Seong Ho Kong, Hyuk-Joon Lee, Woo Ho Kim, Han-Kwang Yang

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Purpose 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. Materials and 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). Conclusion DNA microarray analysis and validation by RT-PCR and TMA showed that overexpression of PAI-1 is related to aggressive LN metastasis in AGC.

Original languageEnglish
Pages (from-to)718-726
Number of pages9
JournalCancer Research and Treatment
Volume47
Issue number4
DOIs
StatePublished - 1 Jan 2015

Keywords

  • Lymph nodes
  • Neoplasm metastasis
  • Oligonucleotide array sequence analysis
  • Plasminogen activator inhibitor 1
  • Stomach neoplasms

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