Jie Cheng1,2, Tim Holland-Letz3, Markus Wallwiener4,5, Harald Surowy6,7, Katarina Cuk6,7, Sarah Schott4, Andreas Trumpp8,9, Klaus Pantel10, Christof Sohn4, Andreas Schneeweiss4,5, Barbara Burwinkel6,7. 1. Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. chengjiehmzx@126.com. 2. Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany. chengjiehmzx@126.com. 3. Department of Biostatistics, German Cancer Research Center (DKFZ), Heidelberg, Germany. 4. Department of Gynecology and Obstetrics, University Women's Clinic, Heidelberg, Germany. 5. National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. 6. Division of Molecular Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7. Molecular Biology of Breast Cancer, Department of Gynecology and Obstetrics, University of Heidelberg, Heidelberg, Germany. 8. Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Heidelberg, Germany. 9. Hi-STEM-Heidelberg Institute for Stem Cell Technology and Experimental Medicine, GmbH, Heidelberg, Germany. 10. Department of Tumor Biology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Abstract
PURPOSE: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis. METHODS: Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients. RESULTS: A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI, 0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration, and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status. CONCLUSIONS: We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBC patients at baseline and during the systematic therapy.
PURPOSE: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis. METHODS: Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients. RESULTS: A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI, 0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration, and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status. CONCLUSIONS: We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBCpatients at baseline and during the systematic therapy.
Entities:
Keywords:
Circulating DNA concentration; Circulating DNA integrity; Circulating tumor cells; Metastatic breast cancer; Prognostic marker
Authors: Ismael da Silva; Rene da Costa Vieira; Carolina Stella; Edson Loturco; André Lopes Carvalho; Carlos Veo; Cristovam Neto; Sandra M Silva; Paulo D'Amora; Marcia Salzgeber; Delcio Matos; Celso R Silva; Jose R Oliveira; Iara Rabelo; Patricia Yamakawa; Rui Maciel; Rosa Biscolla; Maria Chiamolera; Renato Fraietta; Felipe Reis; Marcelo Mori; Dirce Marchioni; Antonio Carioca; Gustavo Maciel; Renato Tomioka; Edmund Baracat; Clovis Silva; Celso Granato; Ricardo Diaz; Bruno Scarpellini; Daniel Egle; Heidi Fiegl; Irmgard Himmel; Christina Troi; Robert Nagourney Journal: Oncotarget Date: 2018-08-03