MicroRNAs accurately identify cancer tissue origin.
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.
Rosenfeld
Nitzan
N
Rosetta Genomics Ltd., Rehovot 76706, Israel.
Aharonov
Ranit
R
Meiri
Eti
E
Rosenwald
Shai
S
Spector
Yael
Y
Zepeniuk
Merav
M
Benjamin
Hila
H
Shabes
Norberto
N
Tabak
Sarit
S
Levy
Asaf
A
Lebanony
Danit
D
Goren
Yaron
Y
Silberschein
Erez
E
Targan
Nurit
N
Ben-Ari
Alex
A
Gilad
Shlomit
S
Sion-Vardy
Netta
N
Tobar
Ana
A
Feinmesser
Meora
M
Kharenko
Oleg
O
Nativ
Ofer
O
Nass
Dvora
D
Perelman
Marina
M
Yosepovich
Ady
A
Shalmon
Bruria
B
Polak-Charcon
Sylvie
S
Fridman
Eddie
E
Avniel
Amir
A
Bentwich
Isaac
I
Bentwich
Zvi
Z
Cohen
Dalia
D
Chajut
Ayelet
A
Barshack
Iris
I
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
D014408:Biomarkers, Tumor; D035683:MicroRNAs