Overexpression of Plasminogen Activator Inhibitor-1 in Advanced Gastric Cancer with Aggressive Lymph Node Metastasis
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Purpose The purpose of this study is to investigate differentially expressed genes using DNA microarraybetween advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasisand that with a more advanced tumor stage but without LN metastasis. Materials and MethodsFive sample pairs of gastric cancer tissue and normal gastric mucosa were taken from threepatients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNAmicroarray experiments were analyzed, and candidate genes were identified using a volcanoplot 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 byreverse-transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, andtissue-microarray (TMA) comprising 47 AGC patients. ResultsCFTR, 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 thesegenes, 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). ConclusionDNA microarray analysis and validation by RT-PCR and TMA showed that overexpression ofPAI-1 is related to aggressive LN metastasis in AGC.
Abstract
Purpose The purpose of this study is to investigate differentially expressed genes using DNA microarraybetween advanced gastric cancer (AGC) with aggressive lymph node (LN) metastasisand that with a more advanced tumor stage but without LN metastasis. Materials and MethodsFive sample pairs of gastric cancer tissue and normal gastric mucosa were taken from threepatients with T3N3 stage (highN) and two with T4N0 stage (lowN). Data from triplicate DNAmicroarray experiments were analyzed, and candidate genes were identified using a volcanoplot 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 byreverse-transcriptase–polymerase chain reaction (RT-PCR) using five AGC patients, andtissue-microarray (TMA) comprising 47 AGC patients. ResultsCFTR, 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 thesegenes, 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). ConclusionDNA microarray analysis and validation by RT-PCR and TMA showed that overexpression ofPAI-1 is related to aggressive LN metastasis in AGC.
참고문헌 (24)
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