MP22-18 IDENTIFICATION OF NOVEL GENE EXPRESSION MARKERS FOR BLADDER CANCER DIAGNOSTICS

Abstract

You have accessJournal of UrologyBladder Cancer: Detection & Screening1 Apr 2014MP22-18 IDENTIFICATION OF NOVEL GENE EXPRESSION MARKERS FOR BLADDER CANCER DIAGNOSTICS Boris Alekseev, Nikolay Vorobyev, Petr Shegay, Anastasia Zabolotneva, Igor Rusakov, Anton Buzdin, Nurshat Gaifullin, and Olga Kovalchuk Boris AlekseevBoris Alekseev More articles by this author , Nikolay VorobyevNikolay Vorobyev More articles by this author , Petr ShegayPetr Shegay More articles by this author , Anastasia ZabolotnevaAnastasia Zabolotneva More articles by this author , Igor RusakovIgor Rusakov More articles by this author , Anton BuzdinAnton Buzdin More articles by this author , Nurshat GaifullinNurshat Gaifullin More articles by this author , and Olga KovalchukOlga Kovalchuk More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.866AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Molecular diagnostics may play key role in developing techniques for the early detection of non-muscle-invasive bladder cancer (BC) and is based on the detection of molecular changes that occur on initial stages of oncological disease. The aim of our study was to identify new potential BC gene expression markers and to evaluate its sensitivity in BC patients. METHODS To identify new gene expression BC markers we performed both bioinformatic and experimental research. For the bioinformatic assays we analysed publically available gene expression data in the Gene Expression Omnibus database. Experimental research consisted in characterization of the gene expression profiles in transitional cell carcinoma (TCC) and normal bladder tissues samples using two alternative approaches: suppression subtractive hybridization (SSH) and microarray hybridization. By using these approaches we have been able to identify 13 novel gene expression markers with area-under-the-curve (AUC) values >0.7 that, to our knowledge, were not associated with TCC in previous studies, but demonstrated a strong correlation with TCC in our tests (p<0,05). Among these entries, there were six top genes with the AUC scores varying from 0.85 to 0.92. To further characterize these novel potential TCC molecular markers, we performed a quantitative RT-PCR (qRT-PCR) assay of the six “top” genes on the 15 normal bladder and 30 surgically-resected TCC samples. RESULTS The transcriptional profiles for ten genes (including five “top” genes): BCL2, CCNE1, CDH1, IGFBP3, STAT1, TRIB1, NUSAP1, PRC1, UBE2C and TFDP1 correlated not only between the experimental and GEO database datasets, but also with the data obtained using SSH. However, the remaining “top” gene, KIFC1, although clearly differential according to our experimental microarray data, demonstrated an intact expression level in the SSH test. The qRT-PCR data confirmed upregulation of the genes: KIFC1, TRIB1, NUSAP1, PRC1, UBE2C, TFDP1, AURKA1 and UHRF1 in the TCC samples. These data suggest that our top six potential BC biomarkers demonstrate strong association with TCC, as reflected by the AUC qRT-PCR values - KIFC1 (0,77), TRIB1 (0,85), NUSAP1 (0,89), PRC1 (0,89), UBE2C (0,91), TFDP1 (0,87). The overall calculated AUC values place them among the best nine known TCC gene expression markers investigated in this study. CONCLUSIONS The top six new gene expression markers - KIFC1, TRIB1, NUSAP1, PRC1, UBE2C and TFDP1 showed excellent sensitivity and reproducibility. Overall, we present a list of potential BC genetic markers possessing a high diagnostic value. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e241-e242 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Boris Alekseev More articles by this author Nikolay Vorobyev More articles by this author Petr Shegay More articles by this author Anastasia Zabolotneva More articles by this author Igor Rusakov More articles by this author Anton Buzdin More articles by this author Nurshat Gaifullin More articles by this author Olga Kovalchuk More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...