Circulating cell-free DNA content as blood based biomarker in endometrial cancer.

// Lucia Cicchillitti 1, * , Giacomo Corrado 2, * , Martina De Angeli 3 , Emanuela Mancini 1 , Ermelinda Baiocco 1 , Lodovico Patrizi 3 , Ashanti Zampa 1 , Roberta Merola 4 , Aline Martayan 4 , Laura Conti 4 , Giulia Piaggio 5, ** and Enrico Vizza 1, ** 1 Department of Experimental Clinical Oncology, Gynecologic Oncology Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy 2 Department of Obstetrics and Gynecology, Gynecologic Oncology Unit, Catholic University of Sacred Heart, Rome, Italy 3 Department of Biomedicine and Prevention, Obstetrics and Gynecology Unit, University of Rome “Tor Vergata”, Rome, Italy 4 Clinical Pathology, IRCCS Regina Elena National Cancer Institute, Rome, Italy 5 Department of Research, Advanced Diagnostics and Technological Innovation, Area of Translational Research, IRCCS Regina Elena National Cancer Institute, Rome, Italy * These authors have contributed equally to this work ** Co-last authors Correspondence to: Giacomo Corrado, email: giacomo.corrado@alice.it Lucia Cicchillitti, email: luciacicchi@gmail.com Keywords: endometrial cancer; circulating cell-free DNA; circulating cell-free mitochondrial DNA; bio-markers; liquid biopsy Received: July 21, 2017      Accepted: December 01, 2017      Published: December 14, 2017 ABSTRACT Background: Altered circulating cell-free DNA (cfDNA) levels are related to cancer development and aggressiveness. Up to now, very few studies have been performed for evaluating cfDNA content in endometrial cancer (EC). Methods: First, we measured cfDNA release in blood serum of EC cancer patients collected before surgery and before the beginning of any treatment by SYBR Gold assay and correlated it with tumor aggressiveness. We also assessed the relative mitochondrial cell-free DNA (cfmtDNA) content by qRT-PCR. Next, we correlated cfDNA levels with BMI, age, hypertension and inflammation markers. Results: CfDNA levels are higher in G2 and G3 compared with G1 EC sera. A significant modulation of cfDNA content was detected in sera from patients with BMI>30 compared with those with BMI<30. We observed a further and significant alteration in cfDNA level in hypertensive patients with G2-G3, but not in G1 EC. Analysis of preoperative neutrophil-to-lymphocyte (NLR) and monocyte-to-lymphocyte (MLR) ratios suggests a contribution of the host response in the altered cfDNA levels in EC. Conclusions: Our data indicate that assessment of total and mitochondrial cfDNA levels in blood sera and the relative NLR and MLR in blood obtained from preoperative patients may help clinical management and prognosis in EC.