Elsevier

Life Sciences

Volume 79, Issue 8, 17 July 2006, Pages 744-748
Life Sciences

Expression of cancer-testis antigen (CTA) in tumor tissues and peripheral blood of Chinese patients with hepatocellular carcinoma

https://doi.org/10.1016/j.lfs.2006.02.024Get rights and content

Abstract

To investigate the expression of cancer-testis antigen (CTA) in Chinese patients with hepatocellular carcinoma (HCC), and the relationship between CTA gene expression and clinical indexes, we used one-step reverse transcription polymerase chain reaction (RT-PCR). The expression of the CTA mRNA was investigated in the tissues of HCC and corresponding peripheral blood of 37 patients with HCC. Fifteen samples of cirrhotic tissues and 15 normal tissues were examined with the same method. Two kinds of CTA (SSX-2 and SSX-5) showed high-specific and high-frequent expression in HCC tissues, but neither of them could be detected in adjacent non-HCC tissues. In corresponding peripheral blood of HCC tissues, the positive expression rate of the SSX-2 and SSX-5 mRNA was not very high. No relationship was found between the expression of CTA and clinical indicators such as age, sex, tumor size, TNM staging, serum AFP level and infection with hepatitis virus. In 15 patients with cirrhosis and 15 other non-tumor patients, none of the SSX-2 and SSX-5 mRNA was detected in liver tissue or peripheral blood. High frequency and specificity of CTAs in HCC indicates that their products may be new potential promising targets for antigen-specific immunotherapy of HCC. High frequent co-expression of the two genes in HCC provides a possibility of polyvalent vaccinations for HCC. Specific expression of CTAs was observed in AFP-negative HCC, suggested applying their mRNA as tumor markers to detect circulating HCC cells as adjuvant diagnostic tool and as indicators of recurrence and prognosis.

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.

Section snippets

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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