Machine-learning algorithms based on personalized pathways for a novel predictive model for the diagnosis of hepatocellular carcinoma

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BACKGROUND: At present, the diagnostic ability of hepatocellular carcinoma (HCC) based on serum alpha-fetoprotein level is limited. Finding markers that can effectively distinguish cancer and non-cancerous tissues is important for improving the diagnostic efficiency of HCC. RESULTS: In this study, we developed a predictive model for HCC diagnosis using personalized biological pathways combined with a machine learning algorithm based on regularized regression and carry out relevant examinations. In two training sets, the overall cross-study-validated area under the receiver operating characteristic curve (AUROC), the area under the precision-recall curve and the Brier score of the diagnostic model were 0.987 [95%confidence interval (CI): 0.979-0.996], 0.981 and 0.091, respectively. Besides, the model showed good transferability in external validation set. In TCGA-LIHC cohort, the AUROC, AURPC and Brier score were 0.992 (95%CI: 0.985-0.998), 0.967 and 0.112, respectively. The diagnostic model has accomplished very impressive performance in distinguishing HCC from non-cancerous liver tissues. Moreover, we further analyzed the extracted biological pathways to explore molecular features and prognostic factors. The risk score generated from a 12-gene signature extracted from the characteristic pathways was correlated with some immune related pathways and served as an independent prognostic factor for HCC. CONCLUSION: We used personalized biological pathways analysis and machine learning algorithm to construct a highly accurate HCC diagnostic model. The excellent interpretable performance and good transferability of this model enables it with great potential for personalized medicine, which can assist clinicians in diagnosis for HCC patients.

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