Dataset Information

Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common human malignancies. Therefore, developing the early, high-sensitivity diagnostic biomarkers to prevent HCC is urgently needed. Serum a-fetoprotein (AFP), the clinical biomarker in current use, is elevated in only ~60% of patients with HCC; therefore, identification of additional biomarkers is expected to have a significant impact on public health. In this study, we used glycan microarray analysis to explore the potential diagnostic value of several cancer-associated carbohydrate antigens (CACAs) as biomarkers for HCC. We used glycan microarray analysis with 58 different glycan analogs for quantitative comparison of 593 human serum samples (293 HCC samples; 133 chronic hepatitis B virus (HBV) infection samples, 134 chronic hepatitis C virus (HCV) infection samples, and 33 healthy donor samples) to explore the diagnostic possibility of serum antibody changes as biomarkers for HCC. Serum concentrations of anti-disialosyl galactosyl globoside (DSGG), anti-fucosyl GM1 and anti-Gb2 were significantly higher in patients with HCC than in chronic HBV infection individuals not in chronic HCV infection patients. Overall, in our study population, the biomarker candidates DSGG, fucosyl GM1 and Gb2 of CACAs achieved better predictive sensitivity than AFP. We identified potential biomarkers suitable for early detection of HCC. Glycan microarray analysis provides a powerful tool for high-sensitivity and high-throughput detection of serum antibodies against CACAs, which may be valuable serum biomarkers for the early detection of persons at high risk for HCC.

SUBMITTER: Wu CS

PROVIDER: S-EPMC3396621 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma.

Wu Chen-Shiou CS Yen Chia-Jui CJ Chou Ruey-Hwang RH Li Shiou-Ting ST Huang Wei-Chien WC Ren Chien-Tai CT Wu Chung-Yi CY Yu Yung-Luen YL

PloS one 20120713 7

Hepatocellular carcinoma (HCC) is one of the most common human malignancies. Therefore, developing the early, high-sensitivity diagnostic biomarkers to prevent HCC is urgently needed. Serum a-fetoprotein (AFP), the clinical biomarker in current use, is elevated in only ~60% of patients with HCC; therefore, identification of additional biomarkers is expected to have a significant impact on public health. In this study, we used glycan microarray analysis to explore the potential diagnostic value o ...[more]

PMID: 22808038

Similar Datasets

Project description:BACKGROUND: Hepatocellular carcinoma (HCC) most commonly develops in patients who have a viral infection, especially in the case of hepatitis B virus (HBV), and in patients with a chronic liver disease. HCC patients with bone metastasis (BM) suffer from pain and other symptoms that significantly reduce their quality of life. Identification of patients who are at high risk for BM after undergoing potentially curative treatment for HCC remains challenging. Here, we aimed to identify HCC BM-related genes and proteins to establish prediction biomarkers. METHODS: RNA was extracted from 48 pairs of intratumoral and peritumoral formalin-fixed, paraffin-embedded tissue from HCC patients with and without BM. A cDNA-mediated annealing, selection, extension and ligation assay containing 502 cancer-related genes was used to identify novel BM-associated genes. An additional independent study with 350 HCC patients who had undergone hepatectomy was conducted to evaluate the expression of candidate genes at the protein level using immunohistochemistry on tissue microarrays (TMAs). Of the 350 patients, 273 (78.0%) were infected with HBV. RESULTS: Seven intratumoral genes and 17 peritumoral genes were overexpressed in patients with BM, whereas 15 intratumoral genes and 28 peritumoral genes were underexpressed in patients with BM. We selected the following four genes for further analysis because they were differentially expressed in the cancer gene-specific microarray and were previously reported to be associated with BM: connective tissue growth factor (CTGF), matrix metalloproteinase-1 (MMP-1), transforming growth factor ?1 (TGF-?1), and interleukin-11 (IL-11). We assessed the protein expression of these selected genes using immunohistochemistry on TMAs including 350 HCC patient specimens. We determined that expression of intratumoral CTGF, intratumoral IL-11, and peritumoral MMP-1 were independent prognostic factors for developing BM in HCC patients. Combining intratumoral CTGF and IL-11 expression was also an independent risk factor for BM development. CONCLUSIONS: Sixty-seven genes were differentially expressed in HCC patients with and without BM. High intratumoral CTGF, positive IL-11, and high peritumoral MMP-1 expression were associated with BM after hepatectomy. Intratumoral CTGF expression combined with IL-11 expression may serve as a useful predictive biomarker for HCC BM.

Project description:Hepatocellular carcinoma (HCC) has a high mortality rate owing to its complexity. Identification of abnormally expressed genes in HCC tissues compared to those in normal liver tissues is a viable strategy for investigating the mechanisms of HCC tumorigenesis and progression as a means of developing novel treatments. A significant advantage of the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) is that the data therein were collected from different independent researchers and may be integrated, allowing for a more robust data analysis. Accordingly, in the present study, the gene expression profiles for HCC and control samples were downloaded from the GEO and TCGA. Functional enrichment analysis was performed using a Metascape dataset, and a protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/proteins (STRING) online database. The prognostic value of mRNA for HCC was assessed using the Kaplan-Meier Plotter, a public online tool. A gene mRNA heatmap and DNA amplification numbers were obtained from cBioPortal. A total of 2,553 upregulated genes were identified. Functional enrichment analysis revealed that these differentially expressed genes (DEGs) were mainly accumulated in metabolism of RNA and the cell cycle. Considering the complexity and heterogeneity of the molecular alterations in HCC, multiple genes for the prognostication of patients with HCC are more reliable than a single gene. Thus, the PPI network and univariate Cox regression analysis were applied to screen candidate genes (small nuclear ribonucleoprotein polypeptide B and B1, nucleoporin 37, Rac GTPase activating protein 1, kinesin family member 20A, minichromosome maintenance 10 replication initiation factor, ubiquitin conjugating enzyme E2 C and hyaluronan mediated motility receptor) that are associated with the overall survival and progression-free survival of patients with HCC. In conclusion, the present study identified a set of genes that are associated with overall survival and progression-free survival of patients with HCC, providing valuable information for the prognosis of HCC.

Dataset Information

Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma.

Publications

Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets