@article {44693,
	title = {Preoperative Cell-Free DNA (cfDNA) in Muscle-Invasive Bladder Cancer Treatment Outcome},
	journal = {Clinical Chemistry},
	volume = {69},
	number = {4},
	year = {2023},
	note = {Papadimitriou, Maria-AlexandraLevis, PanagiotisKotronopoulos, GeorgiosStravodimos, KonstantinosAvgeris, MargaritisScorilas, AndreasengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2023/02/05 06:00Clin Chem. 2023 Apr 3;69(4):399-410. doi: 10.1093/clinchem/hvac218.},
	month = {Apr 3},
	pages = {399-410},
	abstract = {BACKGROUND: Tumor heterogeneity and lack of personalized prognosis leads to bladder cancer (BlCa) patients{\textquoteright} lifelong surveillance with invasive interventions, highlighting the need for modern minimally invasive tools for disease management. Herein, we have evaluated the clinical utility of preoperative serum cell-free DNA (cfDNA) in ameliorating patients{\textquoteright} risk-stratification and prognosis. METHODS: cfDNA was purified from 190 preoperative BlCa patients and 26 healthy individuals{\textquoteright} serum samples and quantified by 2 assays: an in-house quantitative real-time PCR (qPCR) assay using LEP as reference control and a direct fluorometric assay using Qubit HS dsDNA. Capillary electrophoresis was performed in 31 samples for cfDNA fragment profiling. Tumor relapse/progression and metastasis/death were used as clinical endpoints for non-muscle-invasive bladder cancer and muscle-invasive bladder cancer (MIBC), respectively. RESULTS: cfDNA profiling by capillary electrophoresis highlighted that total and fragment-related cfDNA levels were significantly increased in BlCa and associated with advance disease stages. Evaluation of cfDNA levels by both Qubit/qPCR displayed highly consistent results (rs = 0.960; P \&lt; 0.001). Higher cfDNA was correlated with MIBC and stronger risk for early metastasis (Qubit:hazard ratio [HR] = 3.016, P = 0.009; qPCR:HR = 2.918, P = 0.004) and poor survival (Qubit:HR = 1.898, P = 0.042; qPCR:HR = 1.888, P = 0.026) of MIBC patients. Multivariate cfDNA-fitted models led to superior risk stratification and net benefit for MIBC prognosis compared to disease established markers. CONCLUSIONS: Elevated preoperative cfDNA levels are strongly associated with higher risk for short-term metastasis and poor outcome of MIBC, supporting modern noninvasive disease prognosis and management.},
	keywords = {*Cell-Free Nucleic Acids/genetics, *Urinary Bladder Neoplasms/genetics/surgery, Biomarkers, Tumor/genetics, Humans, Neoplasm Recurrence, Local/genetics, Prognosis, Treatment Outcome},
	isbn = {1530-8561 (Electronic)0009-9147 (Linking)},
	author = {Papadimitriou, M. A. and Levis, P. and Kotronopoulos, G. and Stravodimos, K. and Avgeris, M. and Scorilas, A.}
}
