Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis.
- Author:
Yun Suhk SUH
1
;
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
Author Information
- Publication Type:Original Article
- Keywords: Stomach neoplasms; Lymph nodes; Neoplasm metastasis; Plasminogen activator inhibitor 1; Oligonucleotide array sequence analysis
- MeSH: Gastric Mucosa; Humans; Lymph Nodes*; Neoplasm Metastasis*; Oligonucleotide Array Sequence Analysis; Plasminogen Activator Inhibitor 1; Plasminogen Activators*; Plasminogen*; Stomach Neoplasms*
- From:Cancer Research and Treatment 2015;47(4):718-726
- CountryRepublic of Korea
- Language:English
- 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 > or = 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.