title: Accurate molecular classification of renal tumors using microRNA expression.
abstract: Subtypes of renal tumors have different genetic backgrounds, prognoses, and responses to surgical and medical treatment, and their differential diagnosis is a frequent challenge for pathologists. New biomarkers can help improve the diagnosis and hence the management of renal cancer patients. We extracted RNA from 71 formalin-fixed paraffin-embedded (FFPE) renal tumor samples and measured expression of more than 900 microRNAs using custom microarrays. Clustering revealed similarity in microRNA expression between oncocytoma and chromophobe subtypes as well as between conventional (clear-cell) and papillary tumors. By basing a classification algorithm on this structure, we followed inherent biological correlations and could achieve accurate classification using few microRNAs markers. We defined a two-step decision-tree classifier that uses expression levels of six microRNAs: the first step uses expression levels of hsa-miR-210 and hsa-miR-221 to distinguish between the two pairs of subtypes; the second step uses either hsa-miR-200c with hsa-miR-139-5p to identify oncocytoma from chromophobe, or hsa-miR-31 with hsa-miR-126 to identify conventional from papillary tumors. The classifier was tested on an independent set of FFPE tumor samples from 54 additional patients, and identified correctly 93% of the cases. Validation on qRT-PCR platform demonstrated high correlation with microarray results and accurate classification. MicroRNA expression profiling is a very effective molecular bioassay for classification of renal tumors and can offer a quantitative standardized complement to current methods of tumor classification.
authors.affiliation: Department of Pathology, Sheba Medical Center, Ramat-Gan, Israel.
authors.forename: Eddie
authors.initials: E
authors.lastname: Fridman
authors.forename: Zohar
authors.initials: Z
authors.lastname: Dotan
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Miriam Ben
authors.initials: MB
authors.lastname: David
authors.forename: Avital
authors.initials: A
authors.lastname: Dov
authors.forename: Sarit
authors.initials: S
authors.lastname: Tabak
authors.forename: Orit
authors.initials: O
authors.lastname: Zion
authors.forename: Sima
authors.initials: S
authors.lastname: Benjamin
authors.forename: Hila
authors.initials: H
authors.lastname: Benjamin
authors.forename: Hagit
authors.initials: H
authors.lastname: Kuker
authors.forename: Camila
authors.initials: C
authors.lastname: Avivi
authors.forename: Kinneret
authors.initials: K
authors.lastname: Rosenblatt
authors.forename: Sylvie
authors.initials: S
authors.lastname: Polak-Charcon
authors.forename: Jacob
authors.initials: J
authors.lastname: Ramon
authors.forename: Nitzan
authors.initials: N
authors.lastname: Rosenfeld
authors.forename: Yael
authors.initials: Y
authors.lastname: Spector
mesh_terms: D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification* / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs