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Abstract
Background: Cyclooxygenase-2 (COX-2) and transforming growth factor-beta1 (TGF-β1) are modulated in variety cancers including Hepatocellular carcinoma (HCC). However, there is a paucity of data concerning their role in the pathologic process of recurrence of HCC following hepatectomy. We herein assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of HCC diagnosis. Methods: Sixty patients with HCC who underwent curative hepatectomy between 2000 and 2003 were entered in the present study. The immunoreactivity and distribution patterns of COX-2 and TGF-β1 were examined in both the HCC and the adjacent nonHCC tissues of the liver. Risk factors of tumor recurrence within 2 years, including COX-2 and TGF-β1 expression, were investigated by univariate and multivariate analyses. Results: Among 60 patients, 31 patients had early recurrences within 2 years and 14 patients recurred after 2 years following surgery. Patients with low COX-2 expression in the HCC tissues and adjacent nonHCC tissues had favorable disease-free survival (p = 0.002 and p β1 expression in the nonHCC tissues had also longer disease-free survival (p = 0.045). Based on the expression patterns of COX-2 and TGF-β1, patients with low COX-2 and positive TGF-β1 expression in the nonHCC tissues had favorable overall and disease-free survival (p β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy.
Highlights
Surgical resection for hepatocellular carcinoma (HCC) is a widely accepted and safe treatment with a low operative mortality as a result of advances in surgical techniques and peri-operative management [1,2]
We assessed the role of the hepatic expression of COX-2 and TGF-β as predictors for patients with early recurrence within 2 years of Hepatocellular carcinoma (HCC) diagnosis
Increased COX-2 expression and decreased TGF-β1 signaling in nontumor tissues suggested high risk of recurrence and poor survival to the HCC patients following hepatectomy
Summary
Surgical resection for hepatocellular carcinoma (HCC) is a widely accepted and safe treatment with a low operative mortality as a result of advances in surgical techniques and peri-operative management [1,2]. A large number of experimental and clinical studies have established that the TGF-β system can be activated as a tumor suppressor pathway, and that this pathway inhibits cellcycle progression during the G1 phase through the enhanced expression of cyclin-dependent kinase inhibitors such as p21.This signaling activates a tumor suppressor pathway by reversible arrest of cell proliferation [11]. These neoplastic epithelial cells often become resistant to TGF-β-mediated mitoinhibition, and the mechanisms for this alteration during carcinogenesis appear to be influenced by COX-2 expression [12]. A major purpose of the present study was to assess the relation between TGF-β1 and COX-2 expression in the HCC and adjacent nonHCC tissues, and to assess the role of hepatic expression of COX-2 and TGFβ1 as predictors for patients with early recurrence of HCC
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