Dataset Information

Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer.

ABSTRACT:

Background

The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer.

Methods

Tissue samples from a training set and a validation set of patients with gastric adenocarcinoma from China were used for analyses. GalNAc-T5 expression was retrospectively analysed by immunohistochemistry. Results were assessed for association with clinicopathological parameters and overall survival by using Kaplan-Meier analysis. Prognostic values of GalNAc-T5 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating GalNAc-T5 expression was determined by using receiver operating characteristic analysis.

Results

GalNAc-T5 expression was markedly reduced in gastric cancer tissues compared with non-malignant gastric mucosa. Low intratumoral GalNAc-T5 density, which was associated with tumour cell differentiation, T classification, N classification, and TNM stage in the two independent sets, was an independent prognosticator for poor prognosis of gastric cancer patients. Applying the prognostic value of intratumoral GalNAc-T5 density to the conventional clinicopathologic TNM stage system showed a better prognostic value in patients with gastric cancer.

Conclusions

Intratumoral GalNAc-T5 expression was recognised as an independent prognostic marker for the overall survival of gastric cancer patients. Detection of GalNAc-T5 expression in gastric cancer tissues might add some prognostic information for patients with this disease and lead to a more accurate classification under the TNM stage system.

SUBMITTER: He H

PROVIDER: S-EPMC3992513 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer.

He H H Shen Z Z Zhang H H Wang X X Tang Z Z Xu J J Sun Y Y

British journal of cancer 20140311 8

<h4>Background</h4>The family of polypeptide N-acetylgalactosaminyl transferases is responsible for the altered O-linked glycosylation occurring during the development of various cancers and their progression via altering O-glycan biosynthesis. Our studies were designed to investigate the expression and prognostic values of GalNAc-T5 and improve the risk stratification in patients with gastric cancer.<h4>Methods</h4>Tissue samples from a training set and a validation set of patients with gastric ...[more]

PMID: 24619076

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Project description:BackgroundXenograft rejection of pigs organs with an engineered mutation in the GGTA-1 gene (GTKO) remains a predominantly antibody mediated process which is directed to a variety of non-Gal protein and carbohydrate antigens. We previously used an expression library screening strategy to identify six porcine endothelial cell cDNAs which encode pig antigens that bind to IgG induced after pig-to-primate cardiac xenotransplantation. One of these gene products was a glycosyltransferase with homology to the bovine β1,4 N-acetylgalactosaminyltransferase (B4GALNT2). We now characterize the porcine B4GALNT2 gene sequence, genomic organization, expression, and functional significance.MethodsThe porcine B4GALNT2 cDNA was recovered from the original library isolate, subcloned, sequenced, and used to identify a bacterial artificial chromosome (BAC) containing the entire B4GALNT2 locus from the Children's Hospital Oakland Research Institute BACPAC Resource Centre (#AC173453). PCR primers were designed to map the intron/exon genomic organization in the BAC clone. A stable human embryonic kidney (HEK) cell line expressing porcine B4GALNT2 (HEK-B4T) was produced. Expression of porcine B4GALNT2 in HEK-B4T cells was characterized by immune staining and siRNA transfection. The effects of B4GALNT2 expression in HEK-B4T cells was measured by flow cytometry and complement mediated lysis. Antibody binding to HEK and HEK-B4T cells was used to detect an induced antibody response to the B4GALNT2 produced glycan and the results were compared to GTKO PAEC specific non-Gal antibody induction. Expression of porcine B4GALNT2 in pig cells and tissues was measured by qualitative and quantitative real time reverse transcriptase PCR and by Dolichos biflorus agglutinin (DBA) tissue staining.ResultsThe porcine B4GALNT2 gene shares a conserved genomic organization and encodes an open reading frame with 76 and 70% amino acid identity to the human and murine B4GALNT2 genes, respectively. The B4GALNT2 gene is expressed in porcine endothelial cells and shows a broadly distributed expression pattern. Expression of porcine B4GALNT2 in human HEK cells (HEK-B4T) results in increased binding of antibody to the B4GALNT2 enzyme, and increased reactivity with anti-Sd(a) and DBA. HEK-B4T cells show increased sensitivity to complement mediated lysis when challenged with serum from primates after pig to primate cardiac xenotransplantation. In GTKO and GTKO:CD55 cardiac xenotransplantation recipients there is a significant correlation between the induction of a non-Gal antibody, measured using GTKO PAECs, and the induction of antibodies which preferentially bind to HEK-B4T cells.ConclusionThe functional isolation of the porcine B4GALNT2 gene from a PAEC expression library, the pattern of B4GALNT2 gene expression and its sensitization of HEK-B4T cells to antibody binding and complement mediated lysis indicates that the enzymatic activity of porcine B4GALNT2 produces a new immunogenic non-Gal glycan which contributes in part to the non-Gal immune response detected after pig-to-baboon cardiac xenotransplantation.

Dataset Information

Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer.

Background

Methods

Results

Conclusions

Publications

Clinical significance of polypeptide N-acetylgalactosaminyl transferase-5 (GalNAc-T5) expression in patients with gastric cancer.

Similar Datasets

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