MP85-18 CIRCULATING FREE GENOMIC AND MITOCHONDRIAL DNA FRAGMENTS AND THEIR DIAGNOSTIC AND PROGNOSTIC POTENTIAL IN CLEAR CELL RENAL CELL CARCINOMA PATIENTS

Abstract

You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology II1 Apr 2016MP85-18 CIRCULATING FREE GENOMIC AND MITOCHONDRIAL DNA FRAGMENTS AND THEIR DIAGNOSTIC AND PROGNOSTIC POTENTIAL IN CLEAR CELL RENAL CELL CARCINOMA PATIENTS Bernhard Ralla, Luis Hongbiao, Monika Jung, Kilic Ergin, Nils Budach, Annika Fendler, Klaus Jung, and Jonas Busch Bernhard RallaBernhard Ralla More articles by this author , Luis HongbiaoLuis Hongbiao More articles by this author , Monika JungMonika Jung More articles by this author , Kilic ErginKilic Ergin More articles by this author , Nils BudachNils Budach More articles by this author , Annika FendlerAnnika Fendler More articles by this author , Klaus JungKlaus Jung More articles by this author , and Jonas BuschJonas Busch More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2284AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To estimate the association between different circulating cell-free genomic and mitochondrial DNA (cfDNA) fragments and clinico-pathological variables in clear cell renal cell carcinoma (RCC) patients and to evaluate their validity regarding their diagnostic and outcome potential. METHODS The study cohort included 40 healthy controls and 229 RCC patients (145 without metastases before nephrectomy, 84 with metastases before/during targeted therapy). cfDNA was isolated (1 ml EDTA plasma;QIAamp Circulating Nucleic Acid Kit) and qPCR analyses of genomic cfDNA of various gene fragments of amyloid beta (A4) precursor protein (67, 180, 306 bp) and ALU sequences (248/79 bp) and of mitochondrial cfDNA fragments (175/65 bp) were performed. RESULTS The concentrations of the single cfDNA markers partially differed between the study groups while the five integrity indices (long to short fragments) differed between controls and metastatic patients, and two APP indices also to non-metastatic patients. Optimized combinations of different genomic and mitochondrial fragments (binary logistic regression) with two or three assays resulted in areas under the ROC curve of =0.78. In multivariate Cox regression analyses, optimized models for recurrence-free and overall survival were established using the prognostic potential of the individual cfDNA variables combined with the clinicopathological variables. Harrell's C-indices showed distinctly improved prognostic capabilities of these models in comparison to models based only on clinicopathological variables (increase:from 0.725 to 0.827; 0.701 to 0.836). CONCLUSIONS Combinations of genomic and mitochondrial cfDNA are promising tools for urologists in the management of ccRCC patients both in diagnosis and prognosis. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1104-e1105 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Bernhard Ralla More articles by this author Luis Hongbiao More articles by this author Monika Jung More articles by this author Kilic Ergin More articles by this author Nils Budach More articles by this author Annika Fendler More articles by this author Klaus Jung More articles by this author Jonas Busch More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...