Transcriptomic Analysis and Novel Gene Pair-Based Signatures for Hepatitis B-Related Hepatocellular Carcinoma

Abstract

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) misses the opportunity for surgery because it is not detected early. The molecular mechanism of hepatitis B-related liver cancer needs further understanding, and effective diagnostic and prognostic models are in urgent need. Methods: Expression pro les from the Cancer Genome Atlas (TCGA) Liver Hepatocellular Carcinoma (LIHC), GSE121248, GSE94660 GSE76724 from Gene Expression Omnibus (GEO) database were obtained. Differentially expressed genes (DEGs) between normal and tumor HBV-related HCC samples based on GSE121248 and GSE94660. Gene pairs are generated by comparing the expression levels of every two DEGs. A diagnostic signature of pairs of DEGs was built using cross-validation Lasso and Best Subset Selection regression. Hub genes and signi cant modules were screened by Cytoscape, and potential drugs were predicted by DGIdb. A prognostic signature was established and xCell and ssGSEA were utilized to reveal the cell composition and cancer hallmarks to get an elucidation for the risk.Results: 457 DEGs were screened. A powerful diagnostic signature of 2 pairs of DEGs was built and validated in TCGA-LIHC and GEO datasets repeatedly with assured performance. 10 Hub genes were found and fostamatinib was predicted to have potential therapeutic effect on HBV-related HCC. A prognostic signature with good e ciency (Log-rank P value<0.05, AUC=93.1%) were established, with stromal score and several hallmarks related to the risk Conclusion: Taken together, the study provided sight into the molecular mechanism as well as a novel strategy for the early diagnosis and prognosis for HBV-related HCC.