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

Cristiana Lo Nigro, 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

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    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
    Original languageEnglish
    Pages (from-to)1278-1285
    Number of pages8
    JournalJournal of Investigative Dermatology
    Volume133
    Issue number5
    DOIs
    Publication statusPublished - May 2013

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    Nigro, C. L., Wang, H., McHugh, A., Lattanzio, L., Matin, R., Harwood, C., Syed, N., Hatzimichael, E., Briasoulis, E., Merlano, M., Evans, A., Thompson, A., Leigh, I., Fleming, C., Inman, G. J., Proby, C., & Crook, T. (2013). Methylated tissue factor pathway inhibitor 2 (TFPI2) DNA in serum is a biomarker of metastatic melanoma. Journal of Investigative Dermatology, 133(5), 1278-1285. https://doi.org/10.1038/jid.2012.493