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

Abstract

Background and Aim. This exploratory study explored single-stranded DNA (ssDNA) for hepatocellular carcinoma (HCC) diagnosis and prognosis. 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.