Abstract
Hepatocellular carcinoma (HCC) represents the sixth most common cancer worldwide and the third most common cause of cancer-related death. One of the major problems faced by researchers and clinicians in this area is the lack of reliable disease biomarkers, which would allow for an earlier diagnosis, follow-up or prediction of treatment response, among others. In this regard, the “HCC circulome”, defined as the pool of circulating molecules in the bloodstream derived from the primary tumor, represents an appealing target, the so called liquid biopsy. Such molecules encompass circulating tumor proteins, circulating tumor cells (CTCs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), and circulating tumor nucleic acids, namely circulating tumor DNA (ctDNA) and circulating tumor RNA (ctRNA). In this article, we summarize recent findings highlighting the promising role of liquid biopsies as novel potential biomarkers in HCC, emphasizing on its clinical performance.
Highlights
Between 1990 and 2015, the incidence of hepatocellular carcinoma (HCC) increased by 75%, with this type of cancer being accountable roughly for more than 810,000 deaths in 2015 [1,2]
AFP levels can be found elevated in non-HCC patients, including non-cancerous chronic liver diseases, intrahepatic cholangiocarcinoma and metastatic colon cancer [5]
Other circulating protein biomarkers studied in HCC patients include glypican-3 (GPC3), osteopontin, and vascular endothelial growth factor (VEGF)
Summary
Between 1990 and 2015, the incidence of hepatocellular carcinoma (HCC) increased by 75%, with this type of cancer being accountable roughly for more than 810,000 deaths in 2015 [1,2]. Other circulating protein biomarkers studied in HCC patients include glypican-3 (GPC3), osteopontin, and vascular endothelial growth factor (VEGF). The triple combination of AFP/VEGF and α-L-fucosidase (AFU) was associated in this pre-clinical study with a sensitivity of 100% and a specificity of 95% [35] Of note this promising result is lacking so far the needed power, and it could be interesting that it is validated in larger patient cohorts. Osteopontin, ubiquitously expressed in bone and epithelial cells, is highly expressed by tumor cells, including in HCC In this regard, Shang et al reported that OPN alone was associated with good sensitivity and specificity values, the combination of AFP and OPN did slightly improve the predictive sensitivity specificity to 95% and of 96%, respectively. Roberts discussed the drawbacks of AFP and why the AASLD is not in favor of endorsing AFP as a standalone biomarker in their guidelines, partly based on still missing evidence supporting its high sensitivity and specificity as an effective surveillance and diagnostic tool for HCC [40]
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