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Abstract
Hepatocellular carcinoma (HCC) is the one of the leading causes of cancer mortality in the world, mainly due to the difficulty of early detection and limited therapeutic options. The implementation of HCC surveillance programs in well-defined, high-risk populations were only able to detect about 40–50% of HCC at curative stages (Barcelona Clinic Liver Cancer stages 0 & 1) due to the low sensitivities of the current screening methods. The advance of sequencing technologies has identified numerous modifications as potential candidate DNA markers for diagnosis/surveillance. Here we aim to provide an overview of the DNA alterations that result in activation of cancer pathways known to potentially drive HCC carcinogenesis and to summarize performance characteristics of each DNA marker in the periphery (blood or urine) for HCC screening.
Financial & competing interests disclosure
The work was supported by National Institutes of Health R43 CA165312 (WS and YHS), R44 CA165312 (SJ, WS and YHS). S Jain is an employee of JBS Science, Inc. W Song is President and share-holder of JBS-Science, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Writing assistance was provided by A Clemens, JBS Science, Inc.
Key issues
The current methods of surveillance are inadequate and there is an urgent need for better methods.
A non-invasive sensitive approach is critical for surveillance, given the chronic nature of the disease and well-defined high-risk populations.
Due to hepatocellular carcinoma (HCC) heterogeneity, a panel of multiple DNA biomarkers is required for a highly efficacious screening test.
DNA biomarkers are promising screening tools for AFP-negative HCC.
A comprehensive algorithm integrating data from targeted NGS, various risk factors and laboratory tests could be a very powerful tool, not only for HCC screening and molecular diagnosis, but also for personalized management of patients.
