Biomarkers for the Early Detection of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, and the cancer with the fastest increase in mortality in the USA, with more than 39,000 cases and 29,000 deaths in 2018. As with many cancers, survival is significantly improved by early detection. The median survival of patients with early HCC is >60 months but <15 months when detected at an advanced stage. Surveillance of at risk patients improves outcome but fewer than 20% of those at risk for HCC receive surveillance, and current surveillance strategies have limited sensitivity and specificity. Ideally, blood based biomarkers with adequate sensitivity or specificity would be available for early detection of HCC; however, the most commonly used biomarker for HCC, alpha fetoprotein, has inadequate performance characteristics. There are several candidate serum proteomic, glycomic, and genetic markers that have gone through early stages of biomarker validation and have shown promise for the early detection of HCC, but these markers require validation in well curated cohorts. Ongoing prospective cohort studies will permit retrospective longitudinal (phase III biomarker study) validation of biomarkers. In this review, we highlight promising candidate biomarkers and biomarker panels that have completed phase II evaluation but require further validation prior to clinical use.

Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

“…Thus, early HCC diagnosis is critical in order to improve patient outcomes. Proposed strategies for early detection of HCC include adherence to surveillance programs in populations at risk and the development of sensitive and specific diagnostic biomarkers [ 7 , 8 ]. HCC surveillance comprising of ultrasound screening every six months is recommended for all patients with cirrhosis, but, as mentioned above, tailoring HCC surveillance programs may be necessary for certain diseases (i.e., HBV and NAFLD) so to include at-risk non-cirrhotic patients [ 9 ].…”

“…Underlying liver disease is indeed a point of contention as in processes like viral hepatitis; there is an ongoing inflammatory cascade that obscures the approach to identifying immune or inflammatory markers that could be related to the tumor. With new advancing technologies, which allow us to detect low expressing proteins, RNAs and genetic material in endovesicles, a number of new circulating biomarkers are currently under study [ 8 , 13 ]. In this review, we aim to summarize the available information and recent developments on HCC biomarkers detected in serum, classified as protein, miRNA and immune biomarkers ( Figure 1 ), which may impact early HCC diagnosis and, therefore, implementation of appropriate management that can optimize prognosis in HCC.…”

Modeling Hepatocellular Carcinoma Cells Dynamics by Serological and Imaging Biomarkers to Explain the Different Responses to Sorafenib and Regorafenib

“…In this work we describe a novel physic-mathematical model that allowed us to investigate the biological mechanisms of response to TKI in advanced HCC with elevation of AFP and PIVKA-II levels, two of the most studied and validated serological biomarkers already used in clinical practice [ 20 ].…”

The National Cancer Institute Early Detection Research Network: Two Decades of Progress

“…Hepatocellular cancer (HCC) is the leading cause of cancer-related death worldwide related to endemic hepatitis B infection (24). HCC is also the fastest growing cause of cancer-related mortality in the United States due to increasing prevalence of nonalcoholic fatty liver disease, alcohol-related liver disease, and hepatitis C infection (24). HCC generally arises in the context of chronic liver disease where screening has been recommended every 6 months with abdominal ultrasound.…”