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Clinical and prognostic implications of ?1, 6-N-acetylglucosaminyltransferase V in patients with gastric cancer.

ABSTRACT: Aberrant ?1, 6-N-acetylglucosaminyltransferase V (MGAT5) expression in malignant tissues has been reported to be involved in the development of various cancers and their progression, through altering N-glycan branching. We aimed to investigate the clinical and prognostic values of MGAT5 and improve the risk stratification in patients with gastric cancer. MGAT5 expression was retrospectively analyzed by immunohistochemistry in three independent sets comprising 313 patients from China with gastric adenocarcinoma. Results were assessed for association with clinical features and overall survival using Kaplan-Meier analysis. Prognostic values of MGAT5 expression and clinical outcomes were evaluated by Cox regression analysis. A molecular prognostic stratification scheme incorporating MGAT5 expression was determined in patients with late-stage gastric cancer by using receiver operating characteristic analysis. The results show that low intratumoral MGAT5 density, which was associated with poor differentiation, N classification, TNM stage, and Kiel stage, was an independent prognosticator for poor overall survival. The combination of intratumoral MGAT5 expression and TNM or Kiel staging systems had a better predictive power for overall survival. Applying the prognostic value of intratumoral MGAT5 density to TNM stage III+IV and Kiel stage IIIB+IV groups showed a better risk stratification for overall survival in patients with late-stage gastric cancer. In conclusion, integrating intratumoral MGAT5 density that was recognized as an independent prognostic marker into current clinical staging systems significantly improved prognostic stratification of patients with late-stage gastric cancer. This refined risk stratification scheme might aid in appropriate therapeutic options and ultimately improve the outcomes of patients with advanced-stage disease.

SUBMITTER: Wang X

PROVIDER: S-EPMC7657168 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Clinical and prognostic implications of β1, 6-N-acetylglucosaminyltransferase V in patients with gastric cancer.

Wang Xuefei X He Hongyong H Zhang Heng H Chen Weidong W Ji Yuan Y Tang Zhaoqing Z Fang Yong Y Wang Cong C Liu Fenglin F Shen Zhenbin Z Qin Jing J Zhu Yu Y Liu Haiou H Xu Jiejie J Gu Jianxin J Qin Xinyu X Sun Yihong Y

Cancer science 20121206 2

Aberrant β1, 6-N-acetylglucosaminyltransferase V (MGAT5) expression in malignant tissues has been reported to be involved in the development of various cancers and their progression, through altering N-glycan branching. We aimed to investigate the clinical and prognostic values of MGAT5 and improve the risk stratification in patients with gastric cancer. MGAT5 expression was retrospectively analyzed by immunohistochemistry in three independent sets comprising 313 patients from China with gastric ...[more]

PMID: 23107376

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Project description:Background:The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer. Methods:GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 204 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinic-pathological features and prognostic gene signatures, a nomogram was established to predict individual survival probability. Results:GO analysis showed that the 28 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 28 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients. Conclusions:This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.

Project description:BackgroundThe transcription factor Spi-1 proto-oncogene (SPI1, also known as PU.1) is a key regulator of signal communication in the immune system and is essential for the development of myeloid cells and lymphocytes. However, the potential role of SPI1 in gastric cancer (GC) and the correlations between SPI1 and immune infiltration remain unclear.MethodsIn the present study, multiple databases including ONCOMINE, TIMER, Kaplan-Meier Plotter, and The Cancer Genome Atlas were used to explore the expression levels and prognostic value of SPI1 in GC. cBioPortal was used to explore the possible reasons for the increased expression of SPI1 in GC. The correlations between SPI1 expression and tumor-infiltrating immune cells (TICs) were analyzed using CIBERSORT and TIMER. Gene set enrichment analysis was used to determine the biological function of SPI1 in the development of GC. In addition, a risk signature based on SPI1-related immunomodulators was constructed to accurately evaluate the prognosis of patients with GC. The upregulation of SPI1 expression in GC was further confirmed through immunohistochemistry, western blotting, and real-time quantitative PCR (RT-qPCR) assay.ResultsThe expression of SPI1 was increased significantly in GC according to multiple databases, and high expression of SPI1 was related to poor prognosis and progression of GC. The main factor influencing the high expression of SPI1 mRNA in GC may be diploidy, not DNA methylation. Moreover, immunohistochemistry, western blotting, and RT-qPCR assays also confirmed the upregulated expression of SPI1 in GC. CIBERSORT analysis revealed that SPI1 expression was correlated with seven types of TICs (naive B cells, resting memory CD4 T cells, activated memory CD4 T cells, activated natural killer cells, resting natural killer cells, M2 macrophages, and resting dendritic cells). Gene set enrichment analysis indicated that SPI1 might be related to immune activation in GC and participate in cell cycle regulation. In addition, based on SPI1-related immunomodulators, we developed multiple-gene risk prediction signatures and constructed a nomogram that can independently predict the clinical outcome of GC.ConclusionThe results of the present study suggest that SPI1 has a critical role in determining the prognosis of GC patients and may be a potential immunotherapeutic target.

Dataset Information

Clinical and prognostic implications of ?1, 6-N-acetylglucosaminyltransferase V in patients with gastric cancer.

Publications

Clinical and prognostic implications of β1, 6-N-acetylglucosaminyltransferase V in patients with gastric cancer.

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