Uridine phosphorylase 1 is a novel immune‐related target and predicts worse survival in brain glioma

Wang, Jin; Xu, Shi‐Hai; Lv, Wen; Shi, Fei; Mei, Shanshan; Shan, Aijun; Xu, Jiake; Yang, Ying

doi:10.1002/cam4.3251

Cited by 26 publications

(28 citation statements)

References 18 publications

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“…Noushmehr et al identified hypermethylation of UPP1 gene in patients belong to the proneural subgroup that were diagnosed with low grade gliomas and many of the patients were classified to have CIMP-positive tumors [17]. Wang et al found UPP1 gene expression was up-regulated as glioma grade increased using more than 900 samples from the TCGA database [46]. The Gene Ontology analysis revealed that UPP1 is likely associated with immune and inflammatory response and the increase of expression negatively impacted patient survival.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

Weng

Salazar

2021

IJMS

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DNA methylation is an epigenetic change to the genome that impacts gene activities without modification to the DNA sequence. Alteration in the methylation pattern is a naturally occurring event throughout the human life cycle which may result in the development of diseases such as cancer. In this study, we analyzed methylation data from The Cancer Genome Atlas, under the Lower-Grade Glioma (LGG) and Glioblastoma Multiforme (GBM) projects, to identify methylation markers that exhibit unique changes in DNA methylation pattern along with tumor grade progression, to predict patient survival. We found ten glioma grade-associated Cytosine-phosphate-Guanine (CpG) sites that targeted four genes (SMOC1, KCNA4, SLC25A21, and UPP1) and the methylation pattern is strongly associated with glioma specific molecular alterations, primarily isocitrate dehydrogenase (IDH) mutation and chromosome 1p/19q codeletion. The ten CpG sites collectively distinguished a cohort of diffuse glioma patients with remarkably poor survival probability. Our study highlights genes (KCNA4 and SLC25A21) that were not previously associated with gliomas to have contributed to the poorer patient outcome. These CpG sites can aid glioma tumor progression monitoring and serve as prognostic markers to identify patients diagnosed with less aggressive and malignant gliomas that exhibit similar survival probability to GBM patients.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

Weng

Salazar

2021

IJMS

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“…Many other genes have been identified as the mesenchymal subtype’s biomarkers, such as PD1 [ 31 ], PD-L1 [ 32 ], TIM3 [ 33 ], CD163 [ 34 ], PSAP [ 35 ], and UPP1 [ 36 ]. These biomarkers were concurrently enrolled in ROC analysis to assess the sensitivity and specificity of BDKRB2.…”

Section: Resultsmentioning

confidence: 99%

BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma

Yang¹,

Wang

Shi

et al. 2021

Aging

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Bradykinin receptor B2 (BDKRB2) has been reported as an oncogene in several malignancies. In glioma, the role of BDKRB2 remains unknown. This study aimed at investigating its clinical significance and biological function in glioma at the transcriptional level. We selected 301 glioma patients with microarray data from CGGA database and 697 with RNAseq data from TCGA database. Transcriptome and clinical data of 998 samples were analyzed. Statistical analysis and figure generating were performed with R language. BDKRB2 expression showed a positive correlation with the WHO grade of glioma. BDKRB2 was increased in IDH wildtype and mesenchymal subtype of glioma. Gene ontology analysis demonstrated that BDKRB2 was profoundly associated with extracellular matrix organization in glioma. GSEA analysis revealed that BDKRB2 was particularly correlated with epithelial-to-mesenchymal transition (EMT). GSVA analysis showed that BDKRB2 was significantly paralleled with several EMT signaling pathways, including PI3K/AKT, hypoxia, and TGF-β. Moreover, BDKRB2 expression was significantly correlated with key biomarkers of EMT, especially with N-cadherin, snail, slug, vimentin, TWIST1, and TWIST2. Finally, higher BDKRB2 indicated significantly shorter survival for glioma patients. In conclusion, BDKRB2 was associated with more aggressive phenotypes of gliomas. Furthermore, BDKRB2 was involved in the EMT process and could serve as an independent prognosticator in glioma.

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“…Only one bioinformatic analysis of UPP1 expression in gliomas has been published. It indicated that UPP1 expression is positively correlated with the grade of gliomas (46). Finally, because PARVB gene function in GBM has not yet been reported, it was further investigated.…”

Section: Discussionmentioning

confidence: 98%

Construction of Novel Methylation-Driven Gene Model and Investigation of PARVB Function in Glioblastoma

Wang

et al. 2021

Front. Oncol.

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BackgroundGlioblastoma multiforme (GBM) is characterized by widespread genetic and transcriptional heterogeneity. Aberrant DNA methylation plays a vital role in GBM progression by regulating gene expression. However, little is known about the role of methylation and its association with prognosis in GBM. Our aim was to explore DNA methylation-driven genes (DMDGs) and provide evidence for survival prediction and individualized treatment of GBM patients.MethodsUse of the MethylMix R package identified DMDGs in GBM. The prognostic signature of DMDGs based on the risk score was constructed by multivariate Cox regression analysis. Receiver operating characteristics (ROC) curve and C-index were applied to assess the predictive performance of the DMDG prognostic signature. The predictive ability of the multigene signature model was validated in TCGA and CGGA cohorts. Finally, the role of DMDG β-Parvin (PARVB) was explored in vitro.ResultsThe prognostic signature of DMDGs was constructed based on six genes (MDK, NMNAT3, PDPN, PARVB, SERPINB1, and UPP1). The low-risk cohort had significantly better survival than the high-risk cohort (p < 0.001). The area under the curve of the ROC of the six-gene signature was 0.832, 0.927, and 0.980 within 1, 2, and 3 years, respectively. The C-index of 0.704 indicated superior specificity and sensitivity. The six-gene model has been demonstrated to be an independent prognostic factor for GBM. In addition, joint survival analysis indicated that the MDK, NMNAT3, PARVB, SERPINB1, and UPP1 genes were significantly associated with prognosis and therapeutic targets for GBM. Importantly, our DMDG prognostic model was more suitable and accurate for low-grade gliomas. Finally, we verified that PARVB induced epithelial-mesenchymal transition partially through the JAK2/STAT3 pathway, which in turn promoted GBM cell proliferation, migration, and invasion.ConclusionThis study demonstrated the potential value of the prognostic signature of DMDGs and provided important bioinformatic and potential therapeutic target data to facilitate individualized treatment for GBM, and to elucidate the specific mechanism by which PARVB promotes GBM progression.

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Uridine phosphorylase 1 is a novel immune‐related target and predicts worse survival in brain glioma

Cited by 26 publications

References 18 publications

DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

BDKRB2 is a novel EMT-related biomarker and predicts poor survival in glioma

Construction of Novel Methylation-Driven Gene Model and Investigation of PARVB Function in Glioblastoma

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