Article Abstract

SRC-1 and Twist1 are prognostic indicators of liver cancer and are associated with cell viability, invasion, migration and epithelial-mesenchymal transformation of hepatocellular carcinoma cells

Authors: Peng-Wei Zhao, Jia-Wei Zhang, Yan Liu, Yan Liu, Jiang-Wei Liu, Jian-Zhao Huang


Background: Liver cancer is the second leading cause of worldwide cancer-related death, and it has an increasing incidence rate. To investigate the role of SRC-1 and Twist1 in liver cancer and determine their expression in terms of prognosis for patients with liver cancer and in general for hepatocellular carcinoma (HCC) cell lines.
Methods: The present study included a total of 70 patients who underwent liver transplantation or hepatic resection surgeries in our hospital from May 2011 to December 2012. Demographic data and clinical variables as well as alpha-fetoprotein (AFP) and hepatitis B virus (HBV) data were collected. The expression of SRC-1 and Twist1 was determined using immunohistochemistry (IHC). The expression of SRC-1 in different HCC cell lines was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Following SRC-1 silencing by sh-RNA, cell viability, invasion, migration and expression of epithelial- mesenchymal transformation (EMT)-related proteins as well as Twist levels were measured.
Results: The expression of SRC-1 and Twist1 was positively correlated in HCC patients. The expression of SRC-1 differed significantly based on patient tumor diameter, tumor-node-metastasis (TNM) grade, and state of liver cirrhosis, and it also differed in patients with dissimilar tumor metastasis conditions, while the expression of Twist1 in patients was significantly correlated with TNM grade and state of liver cirrhosis as well as by the conditions of tumor metastasis. Survival analysis showed that the expression of both SRC-1 and Twist1 were significantly associated with the overall survival (OS) time of HCC patients. Meanwhile, patients with both SRC-1 (+) and Twist1 (+) tissue had the lowest OS, while patients with both SRC-1 (–) and Twist1 (–) tissue had the highest OS. Cox univariate and multivariate analyzes showed that SRC- 1 expression, tumor stage and liver cirrhosis were independent risk factors for OS time. SRC-1 was highly expressed in HCC cell lines, and inhibition of SRC-1 had a significantly negative impact on cell viability, invasion, migration and EMT; it also inhibited the expression of Twist.
Conclusions: Expression of both Twist1 and SRC-1 were correlated with clinical outcomes and prognoses for HCC patients, and both Twist1 and SRC-1 were independent risk factors for HCC patient survival conditions. Inhibition of SRC-1 suppressed cell proliferation, invasion, migration and EMT of HCC cells, which might be the result of Twist inhibition.

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