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Page 2 of 9 Zhang et al. Hepatoma Res 2019;5:14 I http://dx.doi.org/10.20517/2394-5079.2018.117

worldwide and the second most common cause of cancer-related death in 2015. Hepatitis B virus (HBV)
or hepatitis C virus (HCV) infection accounting for 80%-90% of all HCC cases are well-known major risk
factors for the development of HCC. The other risk factors, such as aflatoxin B1 exposure, alcoholic and
[2,3]
non-alcoholic liver cirrhosis, obesity, diabetes, vitamin D deficiency, are involved in HCC occurrence .
Although treatment with HBV and HCV infection by some recent antiviral therapies is available, virally
[4]
mediated hepatocarcinogenesis is still the etiology for the majority of HCC cases worldwide . In patients
with advanced HCC, there is low response to chemotherapy, and sorafenib is the only standard treatment
[5]
recommended in international guidelines . Thus, it is very important to identify novel diagnosis biomarkers
and therapeutic targets for prognosis of HCC.

Molecular mechanisms of malignant cells will lead to the development of successful HCC therapies.
NcRNAs and epigenetic regulation have been considered as a potential non-invasive biomarkers due to their
experimental and clinical versatility. Whole-genome sequencing analysis has promoted molecular profiles
transduced in expression “signatures” which will help in the comprehension of liver physiopathology. HCC
etiology seems to be a factor that should be included in several clinic association studies.

The development of novel and useful biomarkers can be employed as a screening strategy for early diagnosis
[6]
and prognosis in these high-risk populations, since HCC presents a high mortality rate . Because late
diagnosis, resistance to treatment, tumor recurrence, and metastasis cause to low survival, it is essential
[7]
for developing novel diagnostics and therapeutics of HCC . However, current methods for HCC diagnosis
and therapy have no an optimal accuracy due to the tumor heterogeneity and the frequent late diagnosis.
Therefore, the most urgent needs for early diagnosis and novel therapies of HCC should be developed.

DIAGNOSIS FOR HCC
The present methods for diagnosis of HCC can be divided into the following major aspects: magnetic
resonance imaging, abdominal ultrasonography, and contrast-enhanced computed tomography, liver
biopsy, and serological test. However, the diagnostic effectiveness of above technologies is not very satisfied,
particularly for the diagnosis of small lesions and early diagnosis of HCC. The abdominal ultrasound is an
[8]
operator-dependent test. Liver biopsy is an invasive method not exempt of mortality risk . Therefore, the
serological test should be developed. In this review, we focused on the advances of gene diagnosis for HCC.

MiRNAs serve as HCC diagnostic markers
As we know, cellular miRNAs released into the extracellular circulation system can be detected by
serological test. Owing to circulating miRNAs relevant to HCC, miRNAs may serve as potential biomarkers.
Thus, some circulating miRNAs can be considered as representative of certain pathological conditions.
Moreover, circulating miRNAs possess accessibility well and high stability in the detection system,
[9]
particularly for supervision of early stage, pre-symptomatic diseases in at-risk patients . It has been reported
that a serum diagnostic test, based on a 34-miRNAs signature, can recognize the early stage lung cancer
[10]
with 80% accuracy .
MiRNAs may be used as biomarkers for prognosis or diagnosis in HCC. Down-regulation of miR-let-7g,
miR-22, miR-26, miR-29, miR-99a, miR-124, miR-139, miR-145 and miR-199b is involved in the cell’s life
activities, including proliferation, apoptosis, angiogenesis, disease recurrence, disease-free survival (DFS)
and poor prognosis [11-19] . On the contrary, the increase of miR-10b, miR-17-5p, miR-21, miR-135a, miR-155, miR-182,
miR-221 and miR-222 is taken part in the metastasis, angiogenesis and poor prognosis [20-26] . Additionally,
[27]
miRNA profiling categorizes HCC into three main parts . The above discoveries display the important
value of miRNA detection in prediction of HCC survival. Some microRNAs may be used for HCC diagnosis.
[28]
MiR-101 in serum sample was 95.5% for sensitivity and 90.2% for specificity, respectively . MiR-18a in
[29]
serum sample was 86.1% for sensitivity and 75% for specificity, respectively . The expression of miR-25 was