title: MicroRNAs accurately identify cancer tissue origin.
abstract: MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of unknown primary origin arose, a major clinical problem. We measured miRNA expression levels in 400 paraffin-embedded and fresh-frozen samples from 22 different tumor tissues and metastases. We used miRNA microarray data of 253 samples to construct a transparent classifier based on 48 miRNAs. Two-thirds of samples were classified with high confidence, with accuracy >90%. In an independent blinded test-set of 83 samples, overall high-confidence accuracy reached 89%. Classification accuracy reached 100% for most tissue classes, including 131 metastatic samples. We further validated the utility of the miRNA biomarkers by quantitative RT-PCR using 65 additional blinded test samples. Our findings demonstrate the effectiveness of miRNAs as biomarkers for tracing the tissue of origin of cancers of unknown primary origin.
authors: Rosetta Genomics Ltd., Rehovot 76706, Israel.
authors: Nitzan
authors: N
authors: Rosenfeld
authors: Ranit
authors: R
authors: Aharonov
authors: Eti
authors: E
authors: Meiri
authors: Shai
authors: S
authors: Rosenwald
authors: Yael
authors: Y
authors: Spector
authors: Merav
authors: M
authors: Zepeniuk
authors: Hila
authors: H
authors: Benjamin
authors: Norberto
authors: N
authors: Shabes
authors: Sarit
authors: S
authors: Tabak
authors: Asaf
authors: A
authors: Levy
authors: Danit
authors: D
authors: Lebanony
authors: Yaron
authors: Y
authors: Goren
authors: Erez
authors: E
authors: Silberschein
authors: Nurit
authors: N
authors: Targan
authors: Alex
authors: A
authors: Ben-Ari
authors: Shlomit
authors: S
authors: Gilad
authors: Netta
authors: N
authors: Sion-Vardy
authors: Ana
authors: A
authors: Tobar
authors: Meora
authors: M
authors: Feinmesser
authors: Oleg
authors: O
authors: Kharenko
authors: Ofer
authors: O
authors: Nativ
authors: Dvora
authors: D
authors: Nass
authors: Marina
authors: M
authors: Perelman
authors: Ady
authors: A
authors: Yosepovich
authors: Bruria
authors: B
authors: Shalmon
authors: Sylvie
authors: S
authors: Polak-Charcon
authors: Eddie
authors: E
authors: Fridman
authors: Amir
authors: A
authors: Avniel
authors: Isaac
authors: I
authors: Bentwich
authors: Zvi
authors: Z
authors: Bentwich
authors: Dalia
authors: D
authors: Cohen
authors: Ayelet
authors: A
authors: Chajut
authors: Iris
authors: I
authors: Barshack
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs