Role of ssDNA as a Noninvasive Indicator for the Diagnosis and Prognosis of Hepatocellular Carcinoma: An Exploratory Study

METHODS: This prospective study enrolled 102 patients with newly diagnosed HCC, 21 with cirrhosis, 20 with chronic hepatitis, 284 with nonliver diseases, and 45 healthy individuals at the Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University (May-October 2018). ssDNA was extracted using magnetic beads and quantified using the Qubit ssDNA assay. ssDNA levels were compared among the disease groups and in HCC vs. non-HCC. Receiver operating characteristic (ROC) curves were used to determine the diagnostic value of ssDNA. In patients with resectable HCC, ssDNA and α-fetoprotein (AFP) levels were measured during follow-up and compared with HCC recurrence detected by imaging. RESULTS: The median ssDNA levels were higher in HCC than in healthy individuals, cirrhosis, and chronic hepatitis (median, 23.20 vs. 9.36, 9.64, and 9.76 ng/μL, respectively, P < 0.001). ssDNA levels in HCC were higher than those in cirrhosis and chronic hepatitis (both P < 0.001); there were no differences in ssDNA levels between healthy controls and patients with cirrhosis (P = 0.15) or chronic liver disease (P = 0.39). The area under the curve of ssDNA for HCC diagnosis was 0.909 (95% CI: 0.879-0.933). The ssDNA levels decreased by 3.19-fold (P < 0.001) after HCC radical resection. In six patients, the ssDNA levels increased about 3-6 months before a recurrence was detected by AFP and imaging. CONCLUSIONS: ssDNA might be a noninvasive indicator for HCC diagnosis and prognosis. ssDNA could eventually be complementary to AFP levels and imaging, but confirmatory studies are necessary.