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with the results of Pirisi et al. which showed that the 7 was found predominantly in hepatoma cells and closely
[17]
portal vein thrombosis represented 44% in an autopsied correlated with poor prognosis.
HCC specimen. Another study done by Abdel-Wahab
[18]
et al. documented that only 15.9% had portal vein ROC curve analysis of EGF in HCC showed that the area
thrombosis. This wide range of discrepancy is attributed under the ROC curve of EGF for the prediction of HCC
to the heterogeneity of the studies (some studies progression was 0.93 with 95% CI: 0.89-0.97. Cut-off value
evaluated vascular invasion based on histology while of 450 had 80% sensitivity while cut-off value of 700 had
others evaluated it based only on imaging). Follow-up sensitivity 60.78% and specificity 97% while cut-off value
of our HCC patients for 1 year revealed that the overall of 900 had sensitivity 39.22% and specificity 98%. Shehata
[21]
1-year mortality was 86% with a median survival time of et al. showed that significant higher serum levels of
[19]
8 months. Altekruse et al. reported a median survival EGF in patients with HCC compared to their levels in
of < 5 months although a study in Italy found median patients with HCV infection and control subjects with
survival in an untreated group as 10 months, this could cut-off value of 914 pg/mL, EGF shows 63.3% sensitivity,
[20]
be explained by the fact that the majority of HCC patients and 87.5% specificity for HCC patients.
had more advanced liver disease.
Our results revealed that the EGF serum level increased
Evaluation of serum levels of EGF in the four groups slightly in chronic hepatitis activity than levels in
revealed significantly higher levels of EGF in HCC established cirrhotic group, reflecting potential role of
patients (784.49 ± 313.25 pg/mL) compared to the other EGF in fibrosis process as described by other reports
[29]
three non-HCC groups. These results signified the role of such as Iagoda et al., who studied the growth factors
[21]
EGF in tumor growth and progression. Shehata et al. and the histological picture of the liver in chronic viral
showed higher EGF and transforming growth factor beta hepatitis and hepatic cirrhosis and found that EGF levels
1 levels in patients with HCC compared to the non-HCC decreased with increase in histological activity and the
counterparts with HCV viral infection and the control degree of hepatic fibrosis to cirrhosis. Predictive factors
subjects. In our study, age and serum EGF levels were for progressive HCC in our patients were analyzed by
the only factors that significantly predicted survival in binary logistic regression, serum EGF level was found to
our HCC patients; higher EGF levels may be associated be a predictive factor of HCC progression. These results
with tumor aggressiveness and shortened survival. This agree with the results of a meta-analysis of eight studies
hypothesis is supported by the in vitro findings of Klocke concluding that EGF polymorphism is a risk factor in
et al. who demonstrated that the Ig EGF (secreted hepatocarcinogenesis. Tanabe et al. stated that in
[22]
[30]
[31]
variant of human EGF) imparts immortality to hepatocyte a dose-dependent fashion EGF measurements in serum
in vitro. This also was reported by Inoue et al. who and in liver tissue were presumed to be most relevant
[23]
studied vandetanib, an inhibitor of VEGF receptor-2 and to hepatocyte transformation in cirrhosis and concluded
EGF receptor, in liver cancer in mice and found that it that the EGF gene polymorphism was associated
suppressed tumor development and improved prognosis with development of HCC in liver cirrhosis through
of liver cancer, improved survival, and reduced number modulation of EGF levels. Regarding factors affecting
[24]
of intrahepatic metastases. Yoneda et al. found that patients’ survival using Cox regression analysis, older
higher levels of EGF were associated with activation of age and higher serum EGF levels were the only factors
EGF-EGFR pathway associated with the development significantly affecting survival (P < 0.05).
of CK19-positive HCC, and the EGF-induced increase
in growth abilities of HCC may account for the poor Overall, there was a strong correlation (P < 0.05) between
prognosis of those patients. DeCicco et al. reported EGF level and tumor size, signifying its potential role in
[25]
overexpression of EGF receptors (EGFR) in hepatoma tumor proliferation and its use as a predictive factor of
cells of rats, suggesting that EGFR may be useful as a HCC progression. A major limitation of our study is the
dynamic marker for the development of hepatoma. This relatively small number of patients who underwent TACE,
was confirmed by Sung et al. who concluded that serum heterogeneity of the study cohort is a limitation in many
[26]
EGFR level was a potential biomarker of liver cancer. of the TACE studies because of the wide spectrum of
Kannangai et al. added that EGFR can be considered as HCC patients eligible for TACE compared with the other
[14]
a marker for predicting the metastasis and recurrence of modalities of treatment of HCC, this can be overcome by
HCC. Wu et al. found that EGF was a promoting factor conducting future prospective studies on larger number
[27]
for hepatoma cells stressing on the critical role in EGF- of patients with similar disease. Interestingly, serum EGF
induced proliferation. Wu et al. demonstrated that levels were higher post-TACE, although this difference
[28]
overexpression of epidermal growth factor-like domain was not statistically significant. The explanation of

Hepatoma Research | Volume 2 | Issue 1 | January 15, 2016 23