Abstract
BackgroundWe studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis.MethodsExpressions of Cx43, CD105, and VEGF in 234 HCC tissue specimens were examined using tissue microarray and immunohistochemistry. Cx43 mRNA expression was examined in 38 frozen HCC specimens using RT-PCR. Correlations between these expressions and tumor recurrence, metastasis, and prognosis were analyzed using Kaplan–Meier and Cox regression analyses.ResultsCx43 expression correlated with early tumor recurrence (P = 0.001), disease-free survival (P = 0.026), and overall survival (P = 0.000) in patients with serum AFP < 400 ng/ml, but not in those with serum AFP ≥ 400 μg/L. Cx43 expression is an independent predictor of later recurrence and longer overall survival and is inversely correlated with expression of CD105 and VEGF (P = 0.018 and 0.023, respectively), histological differentiation (P = 0.002), vessel tumor embolism (P = 0.029), and focal number (P = 0.017). Immunohistochemistry showed that Cx43 expression in patients with low AFP was lower in patients with distant metastases than in those with no metastasis or those with liver metastasis. Patients with early recurrence expressed less Cx43 mRNA than did those with no recurrence (χ2 = 9.827, P = 0.002).ConclusionsCx43 expression can delay early HCC recurrence, metastasis, and poor prognosis after radical hepatectomy in patients with HBV-related HCC and low AFP.
Highlights
We studied the relationships among Cx43, CD105, and Vascular endothelial growth factor (VEGF) in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis
Cx43, CD105, and VEGF expression in HBV-related HCC (HBV-HCC) tissues and adjacent or cirrhotic tissues Cx43 appeared in the cytoplasm as brown granules
Cx43- expression in patients with HCC with a low AFP level was significantly associated with a high early recurrence rate and poor prognosis (Table 2), unlike patients with HCC with a high AFP level. These results indicate that for patients with HCC with a low AFP level, Cx43- expression is a likely predictor of early recurrence and a poor prognosis
Summary
We studied the relationships among Cx43, CD105, and VEGF in specimens of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) with different serum AFP levels with respect to recurrence and metastasis. Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections induce approximately 75–80% of HCC in the world [9]. Chronic HBV infection accounts for about 60% of the total liver cancer in developing countries and about 23% of the cancer in developed countries. This infection results in approximately one-third of all cases of liver cirrhosis and more than three-quarters of all cases of HCC worldwide [10]. We confined our investigation of HCC to patients with HBV-related HCC (HBV-HCC) to reduce possible confounding variables, and we plan to study the relationship between and mechanisms of early recurrence of HCC and HBV-related factors (e.g., serum HBV viral load and HBV genotype and mutations)
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