Expression and methylation status of tissue factor pathway inhibitor-2 gene in non-small-cell lung cancer.

Abstract

Tissue factor pathway inhibitor-2 (TFPI-2) is a Kunitz-type serine proteinase inhibitor that inhibits plasmin-dependent activation of several metalloproteinases. Downregulation of TFPI-2 could thus enhance the invasive potential of neoplastic cells in several cancers, including lung cancer. In this study, TFPI-2 mRNA was measured using a real-time PCR method in tumours of 59 patients with non-small-cell lung cancer (NSCLC). Tumour TFPI-2 mRNA levels appeared well correlated with protein expression evaluated by immunohistochemistry and were 4-120 times lower compared to those of nonaffected lung tissue in 22 cases (37%). Hypermethylation of the TFPI-2 gene promoter was demonstrated by restriction enzyme-polymerase chain reaction in 12 of 40 cases of NSCLC (30%), including nine of 17 for whom tumour TFPI-2 gene expression was lower than in noncancerous tissue. In contrast, this epigenetic modification was shown in only three of 23 tumours in which no decrease in TFPI-2 synthesis was found (P=0.016). Decreased TFPI-2 gene expression and hypermethylation were more frequently associated with stages III or IV NSCLC (eight out of 10, P=0.02) and the TFPI-2 gene promoter was more frequently hypermethylated in patients with lymph node metastases (eight out of 16, P=0.02). These results suggest that silencing of the TFPI-2 gene by hypermethylation might contribute to tumour progression in NSCLC.

• Authors: J Rollin, S Iochmann, C Bléchet, F Hubé, S Régina, S Guyétant, E Lemarié, P Reverdiau, Y Gruel
• Journal: British journal of cancer (Br J Cancer) Vol. 92 Issue 4 Pg. 775-83 (Feb 28 2005) ISSN: 0007-0920 [Print] England
• PMID: 15685245 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• DNA, Complementary
• DNA, Neoplasm
• Glycoproteins
• RNA, Messenger
• RNA, Neoplasm
• tissue-factor-pathway inhibitor 2

Topics

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• DNA Methylation
• DNA, Complementary (chemical synthesis)
• DNA, Neoplasm (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Glycoproteins (genetics)
• Humans
• Immunoblotting
• Immunohistochemistry
• Lung Neoplasms (genetics, metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Polymerase Chain Reaction
• Prospective Studies
• RNA, Messenger (metabolism)
• RNA, Neoplasm (metabolism)