Differential Expression of microRNA in Papillary Renal Cell Carcinoma.
Gaurav Sharma, Amber H Hughes, Somak Roy, Maureen A Lyons, Christin M Sciulli, John M Krill-Burger, Lori A Kelly, Sheldon Bastacky, Rajiv Dhir, William A LaFramboise, Anil V Parwani. University of Pittsburgh Medical Center, PA
Background: Micro Ribonucleic Acids (miR) are small non-protein-coding RNAs that bind messenger RNA to post-transcriptionally regulate gene expression impacting cell proliferation, apoptosis and differentiation. Papillary Renal Cell Carcinoma (PRCC) comprises 10 to 15 percent of all RCCs and is subdivided into two types: Type 1 (papillae lined by single layer of cells with low grade nuclear features and scant cytoplasm) and Type 2 (papillae lined by pseudostratified nuclei of higher nuclear grade and abundant eosinophilic cytoplasm). We identified a panel of statistically significant miRs that are differentially expressed in PRCC compared to normal renal tissue consistent with morphological differences between PRCC types.
Design: We selected tumor and adjacent normal renal tissue from 5 cases of Type 1 PRCC, 5 cases of Type 2 PRCC and performed high-throughput microarray (Exiqon, Woburn MA) and quantitative real-time PCR analysis of miR expression levels (TaqMan, AB, Carlsbad CA). The data were subjected to statistical analyses and hierarchical clustering (Partek, St. Louis MO) revealing a discrete set of miRs that exhibited robust statistically significant changes in each PRCC type compared to normal renal tissue and other PRCC type.
Results: Sixteen miRs were differentially expressed amongst the 3 specimen classes. In type 1 PRCC, 4 miRs (including miR-105, p<1.11x10-6 and miR-301b, p < 1.33 x 10-5) were increased 2.3 to 10.5 folds while 3 miRs (including miR-10b, p < 2.91 x 10-4) were decreased. In Type 2 PRCC, 4 miRs (including miR-105, p<3.4x10-5 and miR-21, p<1.44 x 10-5) were increased 3.7 to 6.5 folds while 6 miRs (including miR-136, p< 2.37 x 10-5 and miR-559,p< 1.98 x 10-4) were decreased. miR-105 was common to both types and was increased 10.5 folds in type 1 PRCC and 6.5 folds in type 2 PRCC. The mRNA transcripts representing targets of these sixteen miRs displayed significant correlated expression changes (15 transcripts in type 1 and 32 in type 2) including CASP2, GRB2 (both increased) and NR3C2 (decreased).
Conclusions: In summary, this study indicates the important role of miR expression in regulating mRNA transcription in RCC. Common miR changes may play a role in PRCC formation. However, exclusionary differences in the miR expression profile may provide a basis for discriminating between the two types of PRCC.
Category: Genitourinary (including renal tumors)
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 105, Monday Morning