Genomic landscape of liquid biopsy for hepatocellular carcinoma personalized medicine

Abstract

Hepatocellular carcinoma (HČČ) is the sixth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Advanced-stage HČČ patients have poor survival rates and this requires the discovery of novel clear biomarkers for HČČ early diagnosis and prognosis, identifying risk factors, distinguishing HČČ from non-HČČ liver diseases, and assessment of treatment response. Liquid biopsy has emerged as a novel minimally invasive approach to enable monitoring tumor progression, metastasis, and recurrence. Since the liquid biopsy analysis has relatively high specificity and low sensitivity in cancer early detection, there is a risk of bias. Next-generation sequencing (NGS) technologies provide accurate and comprehensive gene expression and mutational profiling of liquid biopsies including cell-free circulating tumor DNA (ctDNA), circulating tumor cells (ČTČs), and genomic components of extracellular vesicles (EVs) including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Since HČČ is a highly heterogeneous cancer, HČČ patients can display various genomic, epigenomic, and transcriptomic patterns and exhibit varying sensitivity to treatment options. Identification of individual variabilities in genomic signatures in liquid biopsy has the potential to greatly enhance precision oncology capabilities. In this review, we highlight and critically discuss the latest progress in characterizing the genomic landscape of liquid biopsy, which can advance HČČ personalized medicine.