Transcriptome analysis creates a new era of precision medicine for managing recurrent hepatocellular carcinoma

Abstract

The high incidence of hepatocellular carcinoma (HCC) recurrence negatively impacts outcomes of patients treated with curative intent despite advances in surgical techniques and other locoregional liver-targeting therapies. Over the past few decades, the emergence of transcriptome analysis tools, including real-time quantitative reverse transcription PCR, microarrays, and RNA sequencing, has not only largely contributed to our knowledge about the pathogenesis of recurrent HCC but also led to the development of outcome prediction models based on differentially expressed gene signatures. In recent years, the single-cell RNA sequencing technique has revolutionized our ability to study the complicated crosstalk between cancer cells and the immune environment, which may benefit further investigations on the role of different immune cells in HCC recurrence and the identification of potential therapeutic targets. In the present article, we summarized the major findings yielded with these transcriptome methods within the framework of a causal model consisting of three domains: primary cancer cells; carcinogenic stimuli; and tumor microenvironment. We provided a comprehensive review of the insights that transcriptome analyses have provided into diagnostics, surveillance, and treatment of HCC recurrence.

Keywords: Recurrent hepatocellular carcinoma, Microarrays, RNA sequencing, Single-cell RNA sequencing, Precision medicine, Tumor heterogeneity, Tumor microenvironment

Core Tip: The high incidence of hepatocellular carcinoma (HCC) recurrence seriously threatens patient outcomes. This review detailed how various transcriptome profiling methods have contributed to our understanding of recurrent HCC with respect to the carcinogenicity of primary cancer cells, carcinogenic stimuli, and tumor microenvironments, which show great promise in improving the management of HCC.