Genomic Landscape of Liquid Biopsy for Hepatocellular Carcinoma Personalized Medicine

Abstract

Hepatocellular carcinoma (HCC) is the sixth most frequently diagnosed cancer and the third leading cause of cancer-related deaths worldwide. Advanced-stage HCC patients have poor survival rates and this requires the discovery of novel clear biomarkers for HCC early diagnosis and prognosis, identifying risk factors, distinguishing HCC from non-HCC 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 (CTCs), and genomic components of extracellular vesicles (EVs) including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). Since HCC is a highly heterogeneous cancer, HCC patients can display various genomic, epigenomic, and transcriptomic patterns and exhibit varying sensitivity to treatment options. Identification 369 This article is freely accessible online.

Non-Invasive Biomarkers for Immunotherapy in Patients with Hepatocellular Carcinoma: Current Knowledge and Future Perspectives

“…Through autocrine and paracrine mechanisms, exosomes enable the interaction between tumor cells and TME, with immune-modulatory effects and the stimulation of the epithelial to mesenchymal transition that favors vascular invasion and metastatization [ 112 ]. Moreover, increasing evidence suggests that the interaction between tumor-derived exosomes, tumor cells, and TME may play a significant role in the development of drug resistance to TKIs in patients with HCC [ 113 , 114 , 115 , 116 , 117 , 118 ]. The exposure of PD-L1 on exosomes causes the direct inhibition of T cells’ function.…”

“…Exosomes expressing PD-L1 compete with cancer cells and peritumoral cells in binding ICIs; as a result, lower levels of a drug can target tumor cells, resulting in a mechanism of resistance against therapy [ 116 ]. Similar to exosomes, MVs express specific markers on their surface derived from the type of cell that generates them and contain nucleic acids and proteins that could influence several biologic processes [ 117 ]. MVs expressing Hepatocyte Paraffin 1 (HepPar1+) have been found to be higher in patients with HCC than in controls without cancer, and their lack of reduction 3 months after liver resection was observed in patients with tumor recurrence [ 118 ].…”

The Biological Functions and Clinical Values of Exosomal Circular RNAs in Hepatocellular Carcinoma

“…Exosomes produced by tumor cells play a role in epithelial–mesenchymal transition (EMT) and tumor metastasis ( 60 ). Widespread metastases remain a major challenge for therapy and prognosis of HCC ( 2 ).…”

“…Since HCC is a highly heterogeneous cancer, patients with HCC show varying sensitivity to treatment options ( 60 ). Additionally, the high recurrence rate of HCC leads to poor prognosis.…”

The Application of Liquid Biopsy Techniques in High-Risk Population for Hepatocellular Carcinoma

“…89 Exosomes can be internalized by adjacent or distant cells to regulate multiple target genes in recipient cells, they can participate in intercellular communication, and cell microenvironment interactions, and they can mediate cell signaling and metabolism. 94 The characteristics and dynamic changes of exosome cargo molecules directly reflect those of the parental tumor cells, 95 which constitutes the foundation for applying exosomes in cancer diagnosis and prognosis as well as for predicting an individual's response to antitumor therapy. 96 The Composition and Application of Exosomes in HCC…”