A novel prediction model for diagnosing hepatocellular carcinoma in patients with chronic liver disease based on serological biomarkers

Abstract

Background: Hepatocellular carcinoma (HCC), the most common type of digestive cancers, is a common complication of chronic liver disease (CLD). Currently, HCC is often diagnosed by radiological examination. 5-Hydroxymethylcytosine (5hmC) in a vital mammalian DNA epigenetic modification that is found in circulating cell-free DNA (cfDNA) and carries tumor-specific epigenetic information. It may also serve as a potential cancer biomarker for HCC diagnosis. Our study aimed to establish a statistical diagnostic model for diagnosing the risk of HCC in individual patients with CLD according objective tests, especially serological tumor markers. Methods:Based on the 5hmC-seal technique, the genome-wide-5-hydroxymethylcytosine (5hmC) and gene body 5hmC content in cfDNA samples from 96 patients were analyzed. Patients were recruited from the Second Affiliated Hospital of Nanchang University; 64 patients had HCC and 32 patients had CLD. Peripheral blood samples were prospectively collected, followed by blood preparation and cfDNA extraction. Independent risk factors associated with HCC were identified by logistic regression, and a diagnostic model was developed and evaluated based on sensitivity, specificity, and correct diagnostic results. Results:The final model revealed sex, age, 5-Hydroxymethylcytosine (5hmC), and afetoprotein (AFP) as diagnostic indicators in a “discovery” data set. A novel statistical model was formed using the formula: Z = -18.160 + 0.081*age + 1.867*sex + 1.066*(logAFP) + 1.964*(log5hmC), which had an area under the receiver operating curve of 0.973. With 0.7636 as the cutoff point, the model had an estimated sensitivity of 0.891 and a specificity of 0.969. The novel model provides a reliable and stable capacity to predict HCC in patients with CLD. Conclusions: The study findings provide an objective blood serum marker-based model that could enhance the diagnostic efficiency of HCC and form a basis for the early detection of surgically resectable liver cancers in high-risk individuals.