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Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy.

ABSTRACT: Hepatocellular carcinoma (HCC) is the most common cause of cancer-related mortality globally. Since the prognosis of advanced HCC patients is extremely poor, the development of novel molecular targets for diagnosis and therapy is urgently required. In the present study, the expression of the melanoma-associated antigen-D2 (MAGE-D2) gene was investigated to determine whether it affects the malignant phenotype of HCC and thus, may serve as a marker of prognosis. Therefore, the expression of MAGE-D2 mRNA and MAGE-D2 protein in nine HCC cell lines and 151 pairs of surgical tissues was analyzed. mRNA expression levels were analyzed using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry was used to compare the clinicopathological parameters of the tumors. A significant difference in the level of MAGE-D2 expression was observed between the normal liver and chronic hepatitis tissues, however, no significant differences were identified among the levels of the chronic hepatitis, cirrhosis and HCC tissues. The expression patterns of the MAGE-D2 protein were consistent with those of its mRNA. The expression levels of MAGE-D2 mRNA in 66 of 151 (44%) patients were higher in the HCC tissues compared with the corresponding non-cancerous tissues. In addition, the disease-specific survival time was significantly shorter for patients with higher levels of MAGE-D2 mRNA expression. Multivariate analysis identified increased expression of MAGE-D2 mRNA as an independent prognostic factor for disease-specific survival (hazard ratio, 2.65; 95% confidence interval, 1.43-4.98; P=0.002). However, increased expression levels of MAGE-D2 mRNA were not significantly associated with other clinicopathological parameters, including extrahepatic recurrence. These results indicated that MAGE-D2 mRNA affects tumor progression and may serve as a prognostic indicator following curative resection. In addition, MAGE-D2 may provide a target for the therapy of HCC.

SUBMITTER: Hashimoto R

PROVIDER: S-EPMC4314984 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy.

Hashimoto Ryoji R Kanda Mitsuro M Takami Hideki H Shimizu Dai D Oya Hisaharu H Hibino Soki S Okamura Yukiyasu Y Yamada Suguru S Fujii Tsutomu T Nakayama Goro G Sugimoto Hiroyuki H Koike Masahiko M Nomoto Shuji S Fujiwara Michitaka M Kodera Yasuhiro Y

Oncology letters 20141223 3

Hepatocellular carcinoma (HCC) is the most common cause of cancer-related mortality globally. Since the prognosis of advanced HCC patients is extremely poor, the development of novel molecular targets for diagnosis and therapy is urgently required. In the present study, the expression of the melanoma-associated antigen-D2 (<i>MAGE-D2</i>) gene was investigated to determine whether it affects the malignant phenotype of HCC and thus, may serve as a marker of prognosis. Therefore, the expression of ...[more]

PMID: 25663882

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Project description:Background: Hepatocellular carcinoma (HCC) is a tumor with high malignancy and poor 5-years survival rate. Excellent tumor markers are very important for early clinical diagnosis and prognosis evaluation. Previous studies have shown that CDK2AP1 (Cyclin-dependent kinase 2-associated protein 1) is involved in cell-cycle and epigenetic regulation. In the present study, we assess CDK2AP1 expression, prognostic value, immunomodulatory and possible influencing pathways in HCC. Method: The Cancer Genome Atlas (TCGA) database was used to analyse gene expression, clinicopathology and prognosis. The protein level of CDK2AP1 in HCC tissues was detected in the Human Protein Atlas (HPA) database. The immune score in HCC to CDKAP1 expression were analyzed using ESTIMATE. Furthermore, we use Tumor IMmune Estimation Resource (TIMER) database to study CDK2AP1 expression and Immune Infiltration Levels in HCC. Co-expressed genes of CDK2AP1 were predicted and elaborated by LinkedOmics. Results: In normal liver tissues, the expression of CDK2AP1 was significantly lower than tumor tissues, and was correlated with the level of clinical stage and histologic grade in HCC patients. Patients with high expression of CDK2AP1 have a poor prognosis than patients with low CDK2AP1 expression. CDK2AP1 expression level exhibits significantly positive correlations with the number of infiltrating B cells, CD4+ T cells, CD8+ T cells, Macrophages, Neutrophils, and DCs in HCC tissues. KEGG enrichment analysis showed that the related pathways affected by CDK2AP1 mainly include: Fc gamma R-mediated phagocytosis, Th1 and Th2 cell differentiation, Cell cycle, etc. Both in vitro and in vivo experiments confirmed that CDK2AP1 promotes the proliferation and metastasis in hepatocellular carcinoma. Our results highlight the role of CDK2AP1 as an important prognostic indicator and immunotherapy target for HCC patients. Conclusion: We found CDK2AP1 as a new prognostic biomarker for HCC, which could help explain changes in the biological processes and immune environment lead to liver cancer development. Therefore, CDK2AP1 is a potential new target for HCC therapy.

Dataset Information

Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy.

Publications

Aberrant expression of melanoma-associated antigen-D2 serves as a prognostic indicator of hepatocellular carcinoma outcome following curative hepatectomy.

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