MicroRNAs accurately identify cancer tissue origin

• Published in: Nature biotechnology Vol. 26; no. 4; pp. 462 - 469
• Main Authors: Aharonov, Ranit, Barshack, Iris, Rosenfeld, Nitzan, Meiri, Eti, Rosenwald, Shai, Spector, Yael, Zepeniuk, Merav, Benjamin, Hila, Shabes, Norberto, Tabak, Sarit, Levy, Asaf, Lebanony, Danit, Goren, Yaron, Silberschein, Erez, Targan, Nurit, Ben-Ari, Alex, Gilad, Shlomit, Sion-Vardy, Netta, Tobar, Ana, Feinmesser, Meora, Kharenko, Oleg, Nativ, Ofer, Nass, Dvora, Perelman, Marina, Yosepovich, Ady, Shalmon, Bruria, Polak-Charcon, Sylvie, Fridman, Eddie, Avniel, Amir, Bentwich, Isaac, Bentwich, Zvi, Cohen, Dalia, Chajut, Ayelet
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2008; Nature Publishing Group
• Subjects: Agriculture; Base Sequence; Bioinformatics; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cancer; Cancer cells; Care and treatment; Classification; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling - methods; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Life Sciences; Messenger RNA; Metastasis; MicroRNAs - genetics; Miscellaneous; Molecular Sequence Data; Neoplasms - diagnosis; Neoplasms - genetics; Oligonucleotide Array Sequence Analysis - methods; Oncology; Reproducibility of Results; Ribonucleic acid; RNA; Sensitivity and Specificity; Tissues; Tumor Cells, Cultured; Tumors; Micro RNA; Biological marker; Tissue specificity; Metastasis; Malignant tumor; Gene expression; Microarray; Carcinogenesis; Gene silencing; Tissue; Classification; Reverse transcription polymerase chain reaction; Cancer; Quantitative analysis
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt1392

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.