Identification of Platform-Independent Diagnostic Biomarker Panel for Hepatocellular Carcinoma Using Large-Scale Transcriptomics Data.

Abstract

The high mortality rate of hepatocellular carcinoma (HCC) is primarily due to its late diagnosis. In the past, numerous attempts have been made to design genetic biomarkers for the identification of HCC; unfortunately, most of the studies are based on small datasets obtained from a specific platform or lack reasonable validation performance on the external datasets. In order to identify a universal expression-based diagnostic biomarker panel for HCC that can be applicable across multiple platforms, we have employed large-scale transcriptomic profiling datasets containing a total of 2,316 HCC and 1,665 non-tumorous tissue samples. These samples were obtained from 30 studies generated by mainly four types of profiling techniques (Affymetrix, Illumina, Agilent, and High-throughput sequencing), which are implemented in a wide range of platforms. Firstly, we scrutinized overlapping 26 genes that are differentially expressed in numerous datasets. Subsequently, we identified a panel of three genes (, and as HCC biomarker using different feature selection techniques. Three-genes-based HCC biomarker identified HCC samples in training/validation datasets with an accuracy between 93 and 98%, Area Under Receiver Operating Characteristic curve (AUROC) in a range of 0.97 to 1.0. A reasonable performance, i.e., AUROC 0.91-0.96 achieved on validation dataset containing peripheral blood mononuclear cells, concurred their non-invasive utility. Furthermore, the prognostic potential of these genes was evaluated on TCGA-LIHC and GSE14520 cohorts using univariate survival analysis. This analysis revealed that these genes are prognostic indicators for various types of the survivals of HCC patients (e.g., Overall Survival, Progression-Free Survival, Disease-Free Survival). These genes significantly stratified high-risk and low-risk HCC patients (p-value <0.05). In conclusion, we identified a universal platform-independent three-genes-based biomarker that can predict HCC patients with high precision and also possess significant prognostic potential. Eventually, we developed a web server HCCpred based on the above study to facilitate scientific community (http://webs.iiitd.edu.in/raghava/hccpred/).