Integrative multi-omics approach for stratification of tumor recurrence risk groups of Hepatocellular Carcinoma patients

Postoperative tumor recurrence is one of the major concerns associated with the poor prognosis of HCC patients. There is yet to elucidate a standard surveillance system for HCC recurrence risk owing to complexity of this malignancy. Generation of multi-omics data from patients facilitate the identification of robust signatures for various diseases. Thus, the current study is an attempt to develop the prognostic models employing multi-omics data to significantly (p-value <0.05) stratify the recurrence high-risk (median Recurrence Free Survival time (RFS) =<12 months) and low-risk groups (median RFS >12 months). First, we identified key 90RNA, 50miRNA and 50 methylation features and developed prognostic models; attained reasonable performance (C-Index >0.70, HR >2.5), on training and validation datasets. Subsequently, we developed a prognostic (PI) model by integrating the four multi-omics features (SUZ12, hsa-mir-3936, cg18465072, and cg22852503), that are biologically inter-linked with each other. This model achieved reasonable performance on training and validation dataset, i.e. C-Index 0.72, HR of 2.37 (1.61 - 3.50), p-value of 6.72E-06, Brier score 0.19 on training dataset, and C-Index 0.72 (95% CI: 0.63 - 0.80), HR of 2.37 (95% CI: 1.61 - 3.50), p-value of 0.015, Brier score 0.19 on validation dataset. Eventually, Drugbank data was investigated to elucidate therapeutic potential of these signatures. We have identified nine potential drugs against three genes (CA9, IL1A, KCNJ15) that are positively correlated with the tumor recurrence. We anticipate these results from our study will help researchers and clinicians to improve the HCC recurrence surveillance, eventually outcome of patients.