title: Comparison of a healthy miRNome with melanoma patient miRNomes: are microRNAs suitable serum biomarkers for cancer?
abstract: MiRNAs are increasingly recognized as biomarkers for the diagnosis of cancers where they are profiled from tumor tissue (intracellular miRNAs) or serum/plasma samples (extracellular miRNAs). To improve detection of reliable biomarkers from blood samples, we first compiled a healthy reference miRNome and established a well-controlled analysis pipeline allowing for standardized quantification of circulating miRNAs. Using whole miRNome and custom qPCR arrays, miRNA expression profiles were analyzed in 126 serum, whole blood and tissue samples of healthy volunteers and melanoma patients and in primary melanocyte and keratinocyte cell lines. We found characteristic signatures with excellent prognostic scores only in late stage but not in early stage melanoma patients. Upon comparison of melanoma tissue miRNomes with matching serum samples, several miRNAs were identified to be exclusively tissue-derived (miR-30b-5p, miR-374a-5p and others) while others had higher expression levels in serum (miR-3201 and miR-122-5p). Here we have compiled a healthy and widely applicable miRNome from serum samples and we provide strong evidence that levels of cell-free miRNAs only change significantly at later stages of melanoma progression, which has serious implications for miRNA biomarker studies in cancer.
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Christiane
authors.initials: C
authors.lastname: Margue
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Susanne
authors.initials: S
authors.lastname: Reinsbach
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Demetra
authors.initials: D
authors.lastname: Philippidou
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Beaume
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Casandra
authors.initials: C
authors.lastname: Walters
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Jochen G
authors.initials: JG
authors.lastname: Schneider
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.|Klinikum Dortmund GmbH, Germany.
authors.forename: Dorothée
authors.initials: D
authors.lastname: Nashan
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Iris
authors.initials: I
authors.lastname: Behrmann
authors.affiliation: Life Sciences Research Unit, University of Luxembourg, Luxembourg.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kreis
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: circulating miRNAs; healthy miRNome; melanoma biomarkers; miRNA qPCR arrays; serum/tissue samples