Literature DB >> 23407390

Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma.

Cristiana Lo Nigro1, Hexiao Wang, Angela McHugh, Laura Lattanzio, Rubeta Matin, Catherine Harwood, Nelofer Syed, Eleftheria Hatzimichael, Evangelos Briasoulis, Marco Merlano, Alan Evans, Alastair Thompson, Irene Leigh, Colin Fleming, Gareth J Inman, Charlotte Proby, Tim Crook.   

Abstract

Transcriptional silencing of tissue factor pathway inhibitor 2 (TFPI2) occurs in several human tumors including melanoma. We investigated methylated TFPI2 as a biomarker of metastatic melanoma using qRT-PCR to assess TFPI2 expression and pyrosequencing to analyze CpG island methylation in malignant melanoma cell lines, in benign nevi, in 112 primary and metastatic melanomas, and in serum from 6 healthy individuals and 35 patients: 20 patients with primary and 15 patients with metastatic melanoma. The TFPI2 CpG island is unmethylated in nevi but methylation is associated with metastatic melanoma. Circulating methylated TFPI2 DNA is undetectable in sera from healthy individuals and detectable in sera from patients with primary and metastatic melanomas, but the presence of methylated TFPI2 DNA in serum is strongly associated with metastatic disease (P<0.01). Detection of TFPI2-methylated DNA in the serum of patients with resected melanoma is a sensitive and specific biomarker of metastatic melanoma. Confirmation of our results in independent patient cohorts would encourage prospective evaluation as a biomarker of disease state.

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Year:  2013        PMID: 23407390     DOI: 10.1038/jid.2012.493

Source DB:  PubMed          Journal:  J Invest Dermatol        ISSN: 0022-202X            Impact factor:   8.551


  17 in total

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