Dataset Information

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

ABSTRACT:

Background

Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs.

Methods

We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE-A1, MAGE-A3/4, MAGE-A10, MAGE-C1, MAGE-C2, NY-ESO-1, SSX-2, sperm protein 17), onco-fetal (AFP, Glypican-3) and overexpressed tumour antigens (Annexin-A2, Wilms tumor-1, Survivin, Midkine, MUC-1) was determined by immunohistochemistry.

Results

A higher prevalence of MAGE antigens was observed in patients with hepatitis-B. Patients with expression of more tumour antigens in general had better HCC-specific survival (P=0.022). The four tumour antigens with high expression in HCC and no, or weak, expression in surrounding tumour-free-liver tissue, were Annexin-A2, GPC-3, MAGE-C1 and MAGE-C2, expressed in 90, 39, 17 and 20% of HCCs, respectively. Ninety-five percent of HCCs expressed at least one of these four tumour antigens. Interestingly, GPC-3 was associated with SALL-4 expression (P=0.001), an oncofetal transcription factor highly expressed in embryonal stem cells. SALL-4 and GPC-3 expression levels were correlated with vascular invasion, poor differentiation and higher AFP levels before surgery. Moreover, patients who co-expressed higher levels of both GPC-3 and SALL-4 had worse HCC-specific survival (P=0.018).

Conclusions

We describe a panel of four tumour antigens with excellent coverage and good tumour specificity in a western area, low-endemic for hepatitis-B. The association between GPC-3 and SALL-4 is a novel finding and suggests that GPC-3 targeting may specifically attack the tumour stem-cell compartment.

SUBMITTER: Sideras K

PROVIDER: S-EPMC4580401 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

Sideras K K Bots S J SJ Biermann K K Sprengers D D Polak W G WG IJzermans J N M JN de Man R A RA Pan Q Q Sleijfer S S Bruno M J MJ Kwekkeboom J J

British journal of cancer 20150601 12

<h4>Background</h4>Identification of tumour antigens is crucial for the development of vaccination strategies against hepatocellular carcinoma (HCC). Most studies come from eastern-Asia, where hepatitis-B is the main cause of HCC. However, tumour antigen expression is poorly studied in low-endemic, western areas where the aetiology of HCC differs.<h4>Methods</h4>We constructed tissue microarrays from resected HCC tissue of 133 patients. Expression of a comprehensive panel of cancer-testis (MAGE- ...[more]

PMID: 26057582

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Project description:BackgroundA number of case-control patient studies have been conducted to investigate the association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). Despite some controversial reports, it has been suggested that DM is associated with HCC. The previous studies on this subject vary in the selection of populations, sample sizes, methodology, and analysis results. Therefore, it is necessary to further delineate the involvement of DM, together with other related risk factors, in HCC with large sample size and strict analysis methodology.MethodsWe conducted a hospital-based retrospective case-control study at Perking Union Medical College Hospital, China. A total of 1,568 patients with liver diseases were enrolled in the statistical study to evaluate the association of DM and other risk factors with HCC. Among these patients, 716 of them were diagnosed with benign liver diseases, and 852 patients were diagnosed as HCC. We utilized binary logistic regression and stepwise logistic regression to investigate the associations among DM, hypertension, fatty liver, cirrhosis, gallstone, HBV infection, HCV infection, and HCC.ResultsStatistical analysis through the stepwise regression model indicated that the prevalence of DM, male gender, cirrhosis, HCV infection, or HBV infection is higher in the HCC patient group compared to the control group. However, the prevalence of gallstone is negatively associated with HCC cases. DM co-exists with HBV infection, male gender, and age in the HCC cases. Binary logistic regression analysis suggested that DM may synergize with HBV infection in HCC development.ConclusionDM is strongly associated with the increased risk of HCC regardless of the prevalence of HBV infection, HCV infection, cirrhosis, male gender, and age. However, the synergistic interaction between DM and HBV in HCC occurrence is significant. Therefore, DM patients with HBV infection represent a very high HCC risk population and should be considered for HCC close surveillance program.

Dataset Information

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

Background

Methods

Results

Conclusions

Publications

Tumour antigen expression in hepatocellular carcinoma in a low-endemic western area.

Similar Datasets

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