Dataset Information

Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma.

ABSTRACT:

Purpose

ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC).

Patients and methods

Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments.

Results

ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2.

Conclusion

In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.

SUBMITTER: Liu R

PROVIDER: S-EPMC10843983 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Publications

Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma.

Liu Ruijia R Yu Xudong X Cao Xu X Wang Xuyun X Liang Yijun Y Qi Wenying W Ye Yong'an Y Zao Xiaobin X

Journal of inflammation research 20240201

<h4>Purpose</h4>ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC).<h4>Patients and methods</h4>Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were resear ...[more]

PMID: 38318244

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Project description:Background - Hepatocellular carcinomas (HCCs) are heterogeneous tumors with respect to etiology, cell of origin and biology. The course of the disease is unpredictable and is in part dependent on the tumor microenvironment. One of the microenvironmental factors is hypoxia, which is known to promote aggressiveness in other malignant tumors. We hypothesized that certain regions in HCC exist with chronic hypoxia and a characteristic gene expression pattern. Moreover, during the development of HCC there is an important contribution of this chronic hypoxia on prognosis via this gene expression. Until now, most research has been performed in acute hypoxic models (< 24 hours). Methods – Human hepatoblastoma cells HepG2 were cultured in either normoxic (20% O2) or hypoxic (2% O2) conditions for 72 hrs, the time it takes to adapt to chronic hypoxia. After 3 days the cells were harvested and analyzed by microarray technology. The highly significant differentially expressed genes were selected and used to assess the clinical value of our in vitro chronic hypoxia gene signature in four published patient studies. Three of these independent microarray studies on HCC patients were used as training sets to determine a minimal prognostic gene set and one study was used for validation. Gene expression analysis and correlation with clinical outcome was assessed with the bioinfomatic method of Goeman et al (). Results – In the HepG2 cells, 3592 genes were differentially expressed in cells cultured at 2% oxygen for 72 hrs. Out of these, 265 showed a high significant change (2-fold change and p=0.0001). The level of gene expression after 72 hrs was different from the acute hypoxic response (during the first 24 hours) and represented chronicity. Using computational methods we identified 7 out of the 265 highly significant genes that showed correlation with prognosis in all three different training sets and this was independently validated in a 4th dataset. With our approach we could include the largest number of HCC patients in one single study. Conclusion – We identified a 7-gene signature, which is associated with chronic hypoxia and predicts prognosis in patients with HCC. In the future this signature could be used as a diagnostic tool. In addition, chronic hypoxia gene expression information can be used in the search for new therapeutic targets. Two conditions were compared and each sample has a biological replicate. Samples are hybridized in dye-swap, resulting in 4 hybridizations.

Dataset Information

Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma.

Purpose

Patients and methods

Results

Conclusion

Publications

Downregulation of ST6GAL2 Correlates to Liver Inflammation and Predicts Adverse Prognosis in Hepatocellular Carcinoma.

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