The MyD88+ phenotype is an adverse prognostic factor in epithelial ovarian cancer.

Autor: Charles J d'Adhemar, Cathy D Spillane, Michael F Gallagher, Mark Bates, Katie M Costello, Jacqui Barry-O'Crowley, Kathryn Haley, Niamh Kernan, Ciara Murphy, Paul C Smyth, Ken O'Byrne, Stephen Pennington, Aoife A Cooke, Brendan Ffrench, Cara M Martin, Dearbhaile O'Donnell, Bryan Hennessy, Britta Stordal, Stephen Finn, Amanda McCann, Noreen Gleeson, Tom D'Arcy, Brian Flood, Luke A J O'Neill, Orla Sheils, Sharon O'Toole, John J O'Leary
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: PLoS ONE, Vol 9, Iss 6, p e100816 (2014)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0100816
Popis: The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p
Databáze: Directory of Open Access Journals