Hongbiao Lu1, Jonas Busch2, Monika Jung2, Silke Rabenhorst2, Bernhard Ralla2, Ergin Kilic3, Steffen Mergemeier4, Nils Budach5, Annika Fendler6, Klaus Jung7. 1. Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany; Department of Urology, Changzhou No.2 People's Hospital, Jiangsu, China. 2. Department of Urology, University Hospital Charité, Berlin, Germany. 3. Institute of Pathology, University Hospital Charité, Berlin, Germany. 4. CONGEN Biotechnologie GmbH, Berlin, Germany. 5. Department of Radiology, University Hospital Charité, Berlin, Germany. 6. Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany; Department of Signal Transduction, Invasion and Metastasis of Epithelial Cells, Max Delbrück Center of Molecular Medicine, Berlin, Germany. 7. Department of Urology, University Hospital Charité, Berlin, Germany; Berlin Institute for Urological Research, Berlin, Germany. Electronic address: klaus.jung@charite.de.
Abstract
BACKGROUND: There is inconsistent information about the clinical usefulness of circulating cell-free DNA (cfDNA) in plasma from clear cell renal cell cancer (RCC) patients. This is attributed to preanalytical, analytical, and clinical factors that were considered as far as possible in this study. METHODS: cfDNA was extracted from EDTA plasma of healthy people (n=40), non-metastatic (n=145) and metastatic (n=84) RCC patients using the QIAamp Circulating Nucleic Acid Kit. Genomic and mitochondrial cfDNA concentrations were determined using qPCR of different cfDNA fragments (67-306bp). Their diagnostic and prognostic potential was estimated using receiver operating characteristics (ROC) and Cox regression analyses. RESULTS: The 67bp and 180bp genomic cfDNA fragments did not differ between the three study groups while the 306bp fragment was lower in RCC patients than in controls. The mitochondrial cfDNA was higher in metastatic than in non-metastatic patients and controls. The cfDNA integrity indices decreased from controls to metastatic patients. Models built by logistic regression and Cox regression resulted in area under the ROC curves >0.75 and concordance indices of >0.800 in predicting recurrence-free survival and overall survival. CONCLUSION: The study suggests that combinations of cfDNA markers have promising diagnostic and prognostic potential in RCC patients and are worth for further validation in future prospective multicenter studies.
BACKGROUND: There is inconsistent information about the clinical usefulness of circulating cell-free DNA (cfDNA) in plasma from clear cell renal cell cancer (RCC) patients. This is attributed to preanalytical, analytical, and clinical factors that were considered as far as possible in this study. METHODS: cfDNA was extracted from EDTA plasma of healthy people (n=40), non-metastatic (n=145) and metastatic (n=84) RCCpatients using the QIAamp Circulating Nucleic Acid Kit. Genomic and mitochondrial cfDNA concentrations were determined using qPCR of different cfDNA fragments (67-306bp). Their diagnostic and prognostic potential was estimated using receiver operating characteristics (ROC) and Cox regression analyses. RESULTS: The 67bp and 180bp genomic cfDNA fragments did not differ between the three study groups while the 306bp fragment was lower in RCCpatients than in controls. The mitochondrial cfDNA was higher in metastatic than in non-metastatic patients and controls. The cfDNA integrity indices decreased from controls to metastatic patients. Models built by logistic regression and Cox regression resulted in area under the ROC curves >0.75 and concordance indices of >0.800 in predicting recurrence-free survival and overall survival. CONCLUSION: The study suggests that combinations of cfDNA markers have promising diagnostic and prognostic potential in RCCpatients and are worth for further validation in future prospective multicenter studies.
Authors: Ritesh R Kotecha; Erika Gedvilaite; Ryan Ptashkin; Andrea Knezevic; Samuel Murray; Ian Johnson; Natalie Shapnik; Darren R Feldman; Maria I Carlo; Neil J Shah; Marisa Dunigan; Kety Huberman; Ryma Benayed; Ahmet Zehir; Michael F Berger; Marc Ladanyi; Dana W Y Tsui; Robert J Motzer; Chung-Han Lee; Martin H Voss Journal: JCO Precis Oncol Date: 2022-07
Authors: Sanjay R Mehta; Josué Pérez-Santiago; Todd Hulgan; Tyler R C Day; Jill Barnholtz-Sloan; Haley Gittleman; Scott Letendre; Ronald Ellis; Robert Heaton; Stephanie Patton; Jesse D Suben; Donald Franklin; Debralee Rosario; David B Clifford; Ann C Collier; Christina M Marra; Benjamin B Gelman; Justin McArthur; Allen McCutchan; Susan Morgello; David Simpson; James Connor; Igor Grant; Asha Kallianpur Journal: J Neuroinflammation Date: 2017-03-31 Impact factor: 8.322