Marika Piciocchi1, Romilda Cardin1, Alessandro Vitale1, Veronica Vanin1, Anna Giacomin1, Caterina Pozzan1, Gemma Maddalo1, Umberto Cillo1, Maria Guido2, Fabio Farinati3,4. 1. Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy. 2. Department of Medicine, Padova University, Padua, Italy. 3. Department of Surgery, Oncology and Gastroenterology, Padova University, Padua, Italy. fabio.farinati@unipd.it. 4. Department of Surgery, Oncology and Gastroenterology, Policlinico Universitario, Via Giustiniani 2, 35128, Padua, Italy. fabio.farinati@unipd.it.
Abstract
PURPOSE: Circulating free DNA (cfDNA) is an extracellular DNA released in the blood by tumor apoptotic/necrotic cells. cfDNA determination has been proposed as a non-invasive and sensitive marker in the diagnosis of cancer. Our aim was to validate the quantification of cfDNA as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). METHODS: cfDNA was quantified by real-time PCR amplification of the hTERT gene in 142 plasma samples obtained from 66 patients with HCC, 35 with cirrhosis (CIRR) and 41 with advanced HCV-related chronic hepatitis (CH). RESULTS: cfDNA was documented in the plasma of 22 % of the CH patients, 57 % of those with CIRR and 61 % of HCC patients. Its concentration was lower in CH with respect to CIRR and HCC (p = 0.02). A cutoff value in the diagnosis of HCC was calculated by the ROC method (area under the curve 0.69, 91 % sensitivity, 43 % specificity) considering HCC versus CH/CIRR, taken together. Patients with multinodular HCC showed significantly higher levels of cfDNA (p = 0.05). A cutoff value for cfDNA was also calculated for discriminating patients with long or short survival. Survival was significantly longer in patients with cfDNA below than in those above the cutoff value (37 vs. 24 months, p = 0.03). Similar results were obtained in the subgroups of patients with viral or with HCV-only etiology, with slightly higher overall diagnostic accuracy. CONCLUSIONS: The role of the quantitative analysis of cfDNA as a diagnostic test is debatable, but cfDNA levels discriminate patients with more advanced stages of disease, demonstrating a prognostic relevance in patients with HCC.
PURPOSE: Circulating free DNA (cfDNA) is an extracellular DNA released in the blood by tumor apoptotic/necrotic cells. cfDNA determination has been proposed as a non-invasive and sensitive marker in the diagnosis of cancer. Our aim was to validate the quantification of cfDNA as a diagnostic and prognostic tool in hepatocellular carcinoma (HCC). METHODS: cfDNA was quantified by real-time PCR amplification of the hTERT gene in 142 plasma samples obtained from 66 patients with HCC, 35 with cirrhosis (CIRR) and 41 with advanced HCV-related chronic hepatitis (CH). RESULTS: cfDNA was documented in the plasma of 22 % of the CH patients, 57 % of those with CIRR and 61 % of HCC patients. Its concentration was lower in CH with respect to CIRR and HCC (p = 0.02). A cutoff value in the diagnosis of HCC was calculated by the ROC method (area under the curve 0.69, 91 % sensitivity, 43 % specificity) considering HCC versus CH/CIRR, taken together. Patients with multinodular HCC showed significantly higher levels of cfDNA (p = 0.05). A cutoff value for cfDNA was also calculated for discriminating patients with long or short survival. Survival was significantly longer in patients with cfDNA below than in those above the cutoff value (37 vs. 24 months, p = 0.03). Similar results were obtained in the subgroups of patients with viral or with HCV-only etiology, with slightly higher overall diagnostic accuracy. CONCLUSIONS: The role of the quantitative analysis of cfDNA as a diagnostic test is debatable, but cfDNA levels discriminate patients with more advanced stages of disease, demonstrating a prognostic relevance in patients with HCC.
Authors: Annalisa Altimari; Antonia D'Errico Grigioni; Elisa Benedettini; Elena Gabusi; Riccardo Schiavina; Antonio Martinelli; Antonio Maria Morselli-Labate; Giuseppe Martorana; Walter Franco Grigioni; Michelangelo Fiorentino Journal: Am J Clin Pathol Date: 2008-05 Impact factor: 2.493
Authors: K Ishak; A Baptista; L Bianchi; F Callea; J De Groote; F Gudat; H Denk; V Desmet; G Korb; R N MacSween Journal: J Hepatol Date: 1995-06 Impact factor: 25.083
Authors: Rafael Sirera; Roy M Bremnes; Andrea Cabrera; Eloísa Jantus-Lewintre; Elena Sanmartín; Ana Blasco; Nieves Del Pozo; Rafael Rosell; Ricardo Guijarro; José Galbis; José Javier Sánchez; Carlos Camps Journal: J Thorac Oncol Date: 2011-02 Impact factor: 15.609