A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

Xu, Xuyao; Wu, Yue; Jia, Genmei; Zhu, Qiaoying; Li, Dake; Xie, Kaipeng

doi:10.1186/s13048-022-01088-9

Cited by 12 publications

(4 citation statements)

References 87 publications

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“…B4GALT5 is involved in the formation of complex-type N-glycans, which are important for protein folding, stability, and function [27] . Dysregulation of B4GALT5 expression or activity can lead to altered glycosylation patterns, which have been implicated in a variety of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders [28][29][30][31] . For instance, several studies have demonstrated the potential of B4GALT5 downregulation to ameliorate insulin resistance by promoting adipogenic commitment and reducing M1 macrophage in ltration [32] .…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of the miRNA-30a-5p/B4GALT5 axis leads to cell proliferation and is associated with M1 Macrophage Polarization in PNH

zeng

Wang

et al. 2023

Preprint

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Background：MicroRNAs (miRNAs) play diverse roles in various biological processes. However, their role in Paroxysmal Nocturnal Hemoglobinuria (PNH) is not well understood. To investigate the involvement of miRNAs in PNH, we conducted a re-analysis of the GEO database and identified miRNA-30a-5p as the most promising candidate for further mechanism research. Methods: We have constructed a PIGA knock-out K562 cell line and PIGAconditional knock-out mice model by CRISPR/cas9 technology. Furthermore, FACS and colony formation assays were used to clarify proliferative and apoptosis abilities of PNH cells. FACS was used to clarify M1 Macrophage Polarization in mouse bone marrow-derived macrophages (BMDMs). Luciferase assay was used to indicate miRNA target gene. RT-PCR and western blot were used to verify the relationship between miR-30a-5p, B4GALT5 and PI3K/AKT signaling. Results: Our study revealed a significant upregulation of miR-30a-5p in Flaer negative cells compared to Flaer positive cells, in a cohort of 10 PNH patients. Cell colony formation and cell cycle analysis demonstrated that the miRNA-30a-5p mimics group exhibited a higher capacity for proliferation, while the miRNA-30a-5p inhibitor group showed opposite effects. Subsequent luciferase assay results confirmed that miRNA-30a-5p targeted the B4GALT5 gene, which was found to be significantly downregulated in Flaer negative cells from 15 PNH patients. In vitro assays showed that the miRNA-30a-5p/B4GALT5 axis significantly promoted cell proliferation by activating PI3K/AKT signaling. Additionally, our study is the first to describe the polarization state of macrophages in the bone marrow microenvironment of PNH patients, where we observed a higher mean fluorescence intensity (MFI) of CD80 and CD86, markers of M1 macrophages, on macrophages from PNH patients compared to normal controls. Furthermore, siB4GALT5 increased the markers of M1 macrophages in BMDMs, and miRNA-30a-5p inhibitor induced M2-like macrophage polarization, which was markedly reversed in the miRNA-30a-5p inhibition+siB4GALT5 group. Conclusion: Our study has identified that the miRNA-30a-5p targets the B4GALT5 gene, and miRNA-30a-5p/B4GALT5 axis facilitates the proliferation of PNH clones via the PI3K/AKT signaling pathway. Additionally, our findings provide initial evidence that the miRNA-30a-5p/B4GALT5 axis may play a potential role in M1 macrophage polarization in the bone marrow of PNH patients.

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Section: Discussionmentioning

confidence: 99%

Dysregulation of the miRNA-30a-5p/B4GALT5 axis leads to cell proliferation and is associated with M1 Macrophage Polarization in PNH

zeng

Wang

et al. 2023

Preprint

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“…miR-491-5p promotes the progression of acute myeloid leukemia by regulating the expression of B4GALT5 and the PI3K/AKT signaling pathway. The increased mRNA and protein levels of B4GALT5 are associated with poor prognosis for hepatocellular carcinoma, ovarian cancer, cervical cancer and other cancers [ 32 , 33 , 34 , 35 ]. In patients with pancreatic cancer, we discovered that increased B4GALT5 expression was substantially correlated with shorter overall survival.…”

Section: Discussionmentioning

confidence: 99%

Circadian Genes MBOAT2/CDA/LPCAT2/B4GALT5 in the Metabolic Pathway Serve as New Biomarkers of PACA Prognosis and Immune Infiltration

Wang

Zhou

et al. 2023

Life

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Pancreatic cancer (PACA) is a highly malignant tumor with a poor prognosis. Recent studies have discovered substantial differences in the expression levels of several circadian genes in PACA samples compared to normal samples. The goal of this research was to find differentially expressed rhythm genes (DERGs) in PACA samples and determine their role in the development of PACA. A total of 299 DERGs were identified in PACA, including 134 downregulated genes and 165 upregulated genes. DERGs were significantly abundant in the metabolic pathway and immune response pathways, according to GO and KEGG analyses. Survival analyses showed that PACA patients who had higher expression levels of MBOAT2/CDA/LPCAT2/B4GALT5 had shorter overall survival times. Using cell assay verification, the mRNA levels of MBOAT2/CDA/LPCAT2/B4GALT5 in Patu-8988 and PNAC-1 cells were found to be significantly higher than those in HPDE6-C7 cells, which was in line with previous studies on PACA patient data. Through conducting univariate Cox analysis, it was determined that MBOAT2/CDA/LPCAT2/B4GALT5 expression, age and grade were all high-risk factors. The MBOAT2/CDA/LPCAT2/B4GALT5 genes were independently correlated with overall survival, according to the multivariate Cox analysis. The proportion of immune cells in PACA and normal samples significantly changed, according to the immune infiltration analysis. Furthermore, MBOAT2/CDA/LPCAT2/B4GALT5 expression levels were significantly related to the level of immune cell infiltration. The protein–protein interaction network of the MBOAT2/CDA/LPCAT2/B4GALT5 genes included 54 biological nodes and 368 interacting genes. In conclusion, the finding of these DERGs adds to the investigation of the molecular processes underlying the onset and progression of PACA. In the future, DERGs may serve as prognostic and diagnostic biomarkers as well as drug targets for chronotherapy in PACA patients.

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“…Malignant transformation is highly associated with aberrant glycosylation [ 25 ]. Previous studies have found that glycosylation-related genes are associated with the prognosis of patients with breast [ 26 ], ovarian [ 27 ], liver [ 28 ] and cervical cancer [ 29 ]. However, current studies on glycation in PC mainly focus on the influence of individual glycation type or single glycation enzyme on tumor progression [ 30 , 31 ], and there are no relevant reports on the expression status of numerous glycation related genes in PC and their relationship with PC microenvironment [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive prognostic and immune analysis of a glycosylation related risk model in pancreatic cancer

Liu,

Shi,

Tian

et al. 2023

BMC Cancer

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Background Pancreatic cancer (PC) is a malignant tumor with extremely poor prognosis, exhibiting resistance to chemotherapy and immunotherapy. Nowadays, it is ranked as the third leading cause of cancer-related mortality. Glycation is a common epigenetic modification that occurs during the tumor transformation. Many studies have demonstrated a strong correlation between glycation modification and tumor progression. However, the expression status of glycosylation-related genes (GRGs) in PC and their potential roles in PC microenvironment have not been extensively investigated. Method We systematically integrated RNA sequencing data and clinicopathological parameters of PC patients from TCGA and GTEx databases. A GRGs risk model based on glycosylation related genes was constructed and validated in 60 patients from Pancreatic biobank via RT-PCR. R packages were used to analyze the relationships between GRGs risk scores and overall survival (OS), tumor microenvironment, immune checkpoint, chemotherapy drug sensitivity and tumor mutational load in PC patients. Panoramic analysis was performed on PC tissues. The function of B3GNT8 in PC was detected via in vitro experiments. Results In this study, we found close correlations between GRGs risk model and PC patients’ overall survival and tumor microenvironment. Multifaceted predictions demonstrated the low-risk cohort exhibits superior OS compared to high-risk counterparts. Meanwhile, the low-risk group was characterized by high immune infiltration and may be more sensitive to immunotherapy or chemotherapy. Panoramic analysis was further confirmed a significant relationship between the GRGs risk score and both the distribution of PC tumor cells as well as CD8 + T cell infiltration. In addition, we also identified a unique glycosylation gene B3GNT8, which could suppress PC progression in vitro and in vivo. Conclusion We established a GRGs risk model, which could predict prognosis and immune infiltration in PC patients. This risk model may provide a new tool for PC precision treatment.

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A signature based on glycosyltransferase genes provides a promising tool for the prediction of prognosis and immunotherapy responsiveness in ovarian cancer

Cited by 12 publications

References 87 publications

Dysregulation of the miRNA-30a-5p/B4GALT5 axis leads to cell proliferation and is associated with M1 Macrophage Polarization in PNH

Dysregulation of the miRNA-30a-5p/B4GALT5 axis leads to cell proliferation and is associated with M1 Macrophage Polarization in PNH

Circadian Genes MBOAT2/CDA/LPCAT2/B4GALT5 in the Metabolic Pathway Serve as New Biomarkers of PACA Prognosis and Immune Infiltration

Comprehensive prognostic and immune analysis of a glycosylation related risk model in pancreatic cancer

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