MicroRNAs accurately identify cancer tissue origin

被引：738

作者：

Rosenfeld, Nitzan ^{[1
]}

Aharonov, Ranit ^{[1
]}

Meiri, Eti ^{[1
]}

Rosenwald, Shai ^{[1
]}

Spector, Yael ^{[1
]}

Zepeniuk, Merav ^{[1
]}

Benjamin, Hila ^{[1
]}

Shabes, Norberto ^{[1
]}

Tabak, Sarit ^{[1
]}

Levy, Asaf ^{[1
]}

Lebanony, Danit ^{[1
]}

Goren, Yaron ^{[1
]}

Silberschein, Erez ^{[1
]}

Targan, Nurit ^{[1
]}

Ben-Ari, Alex ^{[1
]}

Gilad, Shlomit ^{[1
]}

Sion-Vardy, Netta ^{[2
]}

Tobar, Ana ^{[3
]}

Feinmesser, Meora ^{[3
]}

Kharenko, Oleg ^{[4
]}

Nativ, Ofer ^{[5
]}

Nass, Dvora ^{[6
,7
]}

Perelman, Marina ^{[6
,7
]}

Yosepovich, Ady ^{[6
,7
]}

Shalmon, Bruria ^{[6
,7
]}

Polak-Charcon, Sylvie ^{[6
,7
]}

Fridman, Eddie ^{[6
,7
]}

Avniel, Amir ^{[1
]}

Bentwich, Isaac ^{[1
]}

Bentwich, Zvi ^{[1
]}

Cohen, Dalia ^{[1
]}

Chajut, Ayelet ^{[1
]}

Barshack, Iris ^{[6
,7
]}

机构：

[1] Rosetta Genom Ltd, IL-76706 Rehovot, Israel

[2] Soroka Univ Med Ctr, IL-84101 Beer Sheva, Israel

[3] Beilinson Med Ctr, Rabin Med Ctr, Dept Pathol, IL-49100 Petah Tiqwa, Israel

[4] Tel Aviv Sourasky Med Ctr, Inst Pathol, IL-64239 Tel Aviv, Israel

[5] Bnai Zion Med Ctr, IL-31048 Haifa, Israel

[6] Chaim Sheba Med Ctr, Dept Pathol, IL-52621 Tel Hashomer, Israel

[7] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel

来源：

NATURE BIOTECHNOLOGY | 2008年 / 26卷 / 04期

关键词：

D O I：

10.1038/nbt1392

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 490%. 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.

引用

页码：462 / 469

页数：8

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