e15063 Background: SRY-box containing gene 17 (SOX-17) is implicated in the WNT/β-catenin pathway and acts as a tumor suppressor gene inhibiting the transcription of activated β-catenin. WNT oncogene plays a crucial role in liver carcinogenesis and has been shown to correlate with poor survival and aggressive behavior in hepatocellular carcinoma (HCC). Silencing of SOX-17 gene through promoter hypermethylation results in WNT overexpression. Tumor-related cell free DNA (cfDNA), circulating in the blood of cancer patients can be used for the detection of methylation status of several genes. Therefore, we examined SOX-17 methylation in the blood of HCC patients and correlated it with the outcome. Methods: Patients diagnosed with HCC were eligible. cfDNA from 87 patients (N=87) was isolated from 200 μL serum before any treatment. After DNA extraction, all samples were subjected to a sodium bisulfite conversion reaction. Methylation specific polymerase reaction (MSP) for SOX17 promoter methylation was performed using specific primer pairs for both the methylated and unmethylated promoter sequences. Results: According to BCLC staging system, our patients were staged as A=5 (5.6%), B=15 (17.2%), C=67 (77%) respectively. SOX-17 methylation was detected in 58 (66.7%) patients while 29 (33.3%) had a non-methylated gene. The methylated form of the gene was significantly correlated with an impaired performance status (PS) of 2-4 (p=0.021) and with extrahepatic spread of the disease (p=0.036). No correlation was detected for stage, Child-Pough score of cirrhosis, or underlying cause of HCC. The overall survival (OS) was 14 months for the non-methylated and 5 months for the methylated gene, respectively (p= 0.0062). Sixty three patients received sorafenib as 1st line treatment. The OS was 15 months for patients with the non-methylated and 6 months for patients with the methylated gene, respectively (p= 0.012). In the multivariate analysis for OS, SOX-17 methylation status along with PS remained significant (p=0.04) Conclusions: Assessment of SOX-17 promoter hypermethylation in the peripheral blood is feasible. SOX-17 gene methylation is a frequent event in HCC and seems to correlate with a poorer outcome.