Research abstract

Article abstract

Nature Biotechnology 26, 462 - 469 (2008)
Published online: 23 March 2008 | doi:10.1038/nbt1392

MicroRNAs accurately identify cancer tissue origin

Nitzan Rosenfeld1,8, Ranit Aharonov1,8, Eti Meiri1,8, Shai Rosenwald1,8, Yael Spector1, Merav Zepeniuk1, Hila Benjamin1, Norberto Shabes1, Sarit Tabak1, Asaf Levy1, Danit Lebanony1, Yaron Goren1, Erez Silberschein1, Nurit Targan1, Alex Ben-Ari1, Shlomit Gilad1, Netta Sion-Vardy2, Ana Tobar3, Meora Feinmesser3, Oleg Kharenko4, Ofer Nativ5, Dvora Nass6,7, Marina Perelman6,7, Ady Yosepovich6,7, Bruria Shalmon6,7, Sylvie Polak-Charcon6,7, Eddie Fridman6,7, Amir Avniel1, Isaac Bentwich1, Zvi Bentwich1, Dalia Cohen1, Ayelet Chajut1 & Iris Barshack6,7

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.

  1. Rosetta Genomics Ltd., Rehovot 76706, Israel.
  2. Soroka University Medical Center, Beer-Sheva 84101, Israel.
  3. Department of Pathology, Beilinson Hospital, Rabin Medical Center, Petah-Tikva 49100, Israel.
  4. Pathology Institute, Sourasky Medical Center, Tel Aviv 64239, Israel.
  5. Bnai-Zion Medical Center, Haifa 31048, Israel.
  6. Department of Pathology, Sheba Medical Center, Tel-Hashomer 52621, Israel.
  7. Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
  8. These authors contributed equally to this work.

Correspondence to: Ranit Aharonov1,8 Rosetta Genomics Ltd., Rehovot 76706, Israel (e-mail:

Correspondence to: Iris Barshack6,7 Department of Pathology, Sheba Medical Center, Tel-Hashomer 52621, Israel (e-mail:


These links to content published by NPG are automatically generated.


Integration of virtual and high-throughput screening

Nature Reviews Drug Discovery Review (01 Nov 2002)