Expression of cancer-testis antigen (CTA) in tumor tissues and peripheral blood of Chinese patients with hepatocellular carcinoma
Introduction
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in East Asia. Current treatment options include surgery, ethanol injection, transarterial embolization and chemotherapy, which are effective only in localized tumors. However, the prognosis for patients with HCC remains poor, so identifying and establishing effective novel approaches for the treatment of HCC is a challenge. In recent years immunotherapy has been proposed as a strategy, and active immunotherapy approaches using vaccines derived from defined antigens appear to be especially attractive to treat the patients with HCC. Recently a family of tumor-specific cancer-testis antigens (CTAs) has been identified (Chomez et al., 2001, Chen et al., 2001, Luo et al., 2002). CTA is a family that includes many kinds of tumor-specific antigens which have the feature that they are expressed only in testis and many kinds of tumors (Tajima et al., 2003). More than 50 kinds of CTA have been identified to date, including MAGE, BAGE, GAGE, PAGE, XAGE, NY-ESO-1, SSX, HER-2/neu, SPANX and TRAG-3. MAGE, BAGE and GAGE from melanoma, PAGE from prostate cancer, NY-ESO-1 from esophageal cancer, SSX from synovial sarcoma. The SSX superfamily is one of the important families belonging to CTA. Some studies showed that SSX-1 could be highly expressed in HCC tissues, so searching for more highly and specifically expressed SSX antigens in tumors and using them as targets for immunotherapy become urgent and important for us (Ayyoub et al., 2002, Santos et al., 2000).
There have been many reports about the expression of SSX-1 gene in HCC, but investigations encompassing the SSX-2 and SSX-5 genes together are few. The aim of our research is to investigate the expression of SSX-2 and SSX-5 mRNA in tissue and corresponding peripheral blood of patients with hepatocellular carcinoma, and find the relationship between the expression of SSX mRNA and the different kinds of clinical indexes including diagnosis, prognosis and recurrence, in order to evaluate the possibility of using the antigens as targets for specific immunotherapy of HCC. At the same time through this experiment we want to demonstrate that our markers could become an adjuvant diagnostic tool for determining the prognosis and recurrence of HCC.
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Materials
A total of 36 HCC patients who underwent surgical treatment in our hospital between June 2002 and June 2004 were studied, including hepatectomy or orthotropic liver transplantation, at the First Hospital of Medical College, Qingdao University. The diagnosis of hepatocellular carcinoma was confirmed in all cases by pathology. The 26 male and 10 female patients had a mean age of 53 ± 14.8 y (range 17–79). The hepatitis B surface antigen was positive in 31 cases. Among the 36 cases, anti-HCV was
Blood and tissue sampling
Tissue from liver tumor, cirrhotic and normal liver were obtained during hepatectomy or orthotropic liver transplantation operation and immediately frozen in liquid nitrogen, then stored at − 80 °C until the extraction of total RNA. Approximately 80–100 mL of peripheral blood was drawn just before the operation started. All blood samples were heparin-treated to prevent coagulation. Blood mononuclear cells (MNC) were isolated by density gradient centrifugation through lymphocytic separating
Expression of SSX-2 and SSX-5 antigen genes in HCC tissues
Among the 36 HCC tissues investigated, SSX-2 and SSX-5 mRNA was expressed positively in 36.1% (13 / 36) and 47.2% (17 / 36) of the samples from HCC patients, respectively. Both of them were expressed positively in 6 cases (16.7%). At least one CT antigen mRNA was positive in 72.2% (26 / 36) of HCC tissues. Conversely, no CT antigen mRNA could be detected in the corresponding tissues adjacent to HCC. In addition, none of samples of 15 cirrhotic and 15 normal liver tissues expressed SSX-2 or SSX-5 mRNA.
Discussion
HCC is one of the most common cancers of the world with relatively low survival rate. Its clinical syndrome is not very conspicuous and it has a rapid development. Until to now, HCC treatment options have been limited to surgery and local ablative therapy. The results of above therapy are not satisfactory, and immunotherapy for carcinoma is one of the alternative approaches that have not yet been studied in detail in HCC. Many kinds of cancer-testis antigens, such as MAGE-1, MAGE-2, MAGE-3,
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