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Liu et al. Novel predictive and prognostic strategies of HBV-related HCC

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of tumor recurrence. [74] Therefore, EpCAM CTCs CONCLUSION
may be used as a real-time parameter for monitoring
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treatment response. In addition, EpCAM CTCs are HBV-induced HCC is a common malignancy
positive in HCC patients with different BCLC stages characterized by high mortality, high recurrence
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and the positive rates of EpCAM CTCs in patients of rate, and significant heterogeneity. Cancer Evo-
BCLA stage A, B, and C are 11.1%, 19.4%, and 57.9%, Dev, a novel scientific theory of HBV-induced
+
respectively. [75] Thus, EpCAM CTC is prognostic and carcinogenesis, provides an evolutionary insight of
predictive in HCC. HCC occurrence/recurrence prediction. From this
point of view, recent development of HCC predictive
Cell-free DNA and prognostic strategies can be categorized as
Biopsy of HCC may be restricted by the special three main directions: evaluating the inflammatory
position of tumors or the poor condition of patients, microenvironment of cancer evolution via investigating
resulting in the limitation of HCC gene analysis for HBV variables and characteristics of immune
prognostic and predictive purposes. [76] The necrosis imbalance, identifying alteration patterns of signaling
and apoptosis of tumor cells usually release cell-free transformation through signatures of gene expression
DNA (cfDNA) into circulation. Based on sequencing and somatic mutation, and detecting cells with
technology, genetic and epigenetic information can malignancy potential and their hallmarks in peripheral
blood. To validate predictive or prognostic biomarkers,
be obtained from these cfDNA. Detecting cfDNA is 4 steps should be taken: (1) exploratory research,
a microinvasive method to find early HCC, termed to discover promising biomarkers; (2) case-control
as “liquid biopsy”. [77] The abnormities including study, to evaluate statistical association between the
methylation changes and point mutations in cfDNA occurrence/recurrence and biomarkers; (3) cohort
can be detected in peripheral blood even before the study, to validate the sensitivity and specificity of
solid tumor nidus can be detected.
biomarkers; (4) randomized clinical control trail, to
determine if the screening and related prophylaxis/
Hypermethylated RASSF1A within cfDNA sequence treatment can reduce the occurrence/recurrence.
is present in the sera of 93% HCC patients. When Currently, most novel biomarkers were just validated
combining RASSF1A methylation and AFP to in phase 2 or 3. Further validation and reasonable
diagnose HCC, the sensitivity and specificity increase combination of novel biomarkers should be conducted
from 65% and 87% using AFP alone to 77% and 89%, under the direction of Cancer Evo-Dev theory.
respectively. Serum methylated RASSF1A is also
prognostic and also reflects the tumor load in HCC Financial support and sponsorship
patients. [78] A study with a cohort of 151 HCC patients
indicated that 4 hypermethylation genes (RGS10, This work was supported by grants from the
ST8SIA6, RUNX2, and VIM) in sera have weak National Key Basic Research Program (Grant No.
2015CB554006). The study sponsors had no role
correlation with each other but the combination of the
4 genes as a classifier successfully identified HCC in the writing of the manuscript or in the decision to
patients from HBV-induced cirrhosis population, with submit the manuscript for publication.
the sensitivity of 85% and the specificity of 96%. [79]
Conflicts of interest
TP53 R249S mutation in cfDNA was proved to have a There are no conflicts of interest.
remarkable ecological correlation with HCC exposure
in China and Africa. [80] In a retrospective study using Patient consent
short oligonucleotide mass analysis to exam R249S There is no patient involved.
in the plasma ahead of cancer diagnosis, 9 (64%) of
14 patients who developed HCC during the follow- Ethics approval
up were positive for R249S. [81] Genetic mutation This review is waived for ethical approval.
in serum is related to the mutation in tumor tissue.
Another study examining the mutations of CTNNB1, REFERENCES
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