In this study, we performed a comprehensively analysis of gene expression and DNA methylation data to establish diagnostic, prognostic, and recurrence models for hepatocellular carcinoma (HCC).

Methods: We collected gene expression and DNA methylation datasets for over 1,200 clinical samples. Integrated analyses of RNA-sequencing and DNA methylation data were performed to identify DNA methylation-driven genes. These genes were utilized in univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to build a prognostic model. Recurrence and diagnostic models for HCC were also constructed using the same genes.

Results: A total of 123 DNA methylation-driven genes were identified. Two of these genes (SPP1 and LCAT) were chosen to construct the prognostic model. The high-risk group showed a markedly unfavorable prognosis compared to the low-risk group in both training (HR= 2.81; P< 0.001) and validation (HR= 3.06; P< 0.001) datasets. Multivariate Cox regression analysis indicated the prognostic model to be an independent predictor of prognosis (P< 0.05). Also, the recurrence model successfully distinguished the HCC recurrence rate between the high-risk and low-risk groups in both training (HR= 2.22; P< 0.001) and validation (HR= 2; P< 0.01) datasets. The two diagnostic models provided high accuracy for distinguishing HCC from normal samples and dysplastic nodules in the training and validation datasets, respectively.

Conclusions: We identified and validated prognostic, recurrence, and diagnostic models that were constructed using two DNA methylation-driven genes in HCC. The results obtained by integrating multidimensional genomic data offer novel research directions for HCC biomarkers and new possibilities for individualized treatment of patients with HCC.