Identification of Secreted Phosphoprotein 1 (SPP1) as a Prognostic Factor in Lower-Grade Gliomas

Chen, Jiawei; Hou, Chongxian; Zheng, Zongtai; Lin, Han; Lv, Guangzhao; Zhou, Dong

doi:10.1016/j.wneu.2019.06.219

Cited by 19 publications

(15 citation statements)

References 65 publications

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“…Reports showed that the Engrailed 1 (EN1), a member of homeobox-containing transcription factors, can be used as a prognostic marker in LGG patients (28). Besides, the over-expression of selected phosphoprotein 1 (SPP1), an B A important extracellular glycoprotein, was related to worse overall survival in LGG (29). However, there is little research clarifying the relationship between the GPX1 expression and prognostic potential in LGG.…”

Section: Discussionmentioning

confidence: 99%

Expression and prognostic potential of GPX1 in human cancers based on data mining

Wei¹,

Qiu²,

Xu³

et al. 2020

Ann Transl Med

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Background: Glutathione peroxidase-1 (GPX1) is a member of the GPX family, which considered an enzyme that interacts with oxidative stress. GPX1 differential expression is closely correlated with carcinogenesis and disease progression. In this study, we used bioinformatics analysis to investigate GPX1 expression level and explore the prognostic information in different human cancers. Methods: Expression was analyzed via the Oncomine database and Gene Expression Profiling InteractiveAnalysis tool, and potential prognostic analysis was evaluated using the UALCAN, GEPIA, and DriverDBv3 databases. Then, the UALCAN database was used to find the promoter methylation of GPX1 in defied cancer types. While GPX1 related functional networks were found within the GeneMANIA interactive tool and Cytoscape software. Moreover, Metascape online website was used to analyze Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results: We found that GPX1 was commonly overexpressed in most human cancers. High expression of GPX1 could lead to poor outcomes in Brain Lower Grade Glioma, while GPX1 over expression was correlated with better prognosis in Kidney renal papillary cell carcinoma (KIPP). High GPX1 expression was marginally associated with poor prognosis in acute myeloid leukemia (AML). Gene regulation network suggested that GPX1 mainly involved in pathways including the glutathione metabolism, ferroptosis, TP53 regulates metabolic genes, reactive oxygen species (ROS) metabolic process, and several other signaling pathways.Conclusions: Our findings revealed that GPX1 showed significant expression differences among cancers and served as a prognostic biomarker for defined cancer types. The data mining effectively revealed useful information about GPX1 expression, prognostic values, and potential functional networks in cancers, thus providing researchers with an available way to further explore the mechanism underlying carcinogenesis of genes of interest in different cancers.

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Section: Discussionmentioning

confidence: 99%

Expression and prognostic potential of GPX1 in human cancers based on data mining

Wei¹,

Qiu²,

Xu³

et al. 2020

Ann Transl Med

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“…Interestingly, the concentration of SPP1 in the peripheral blood of our patients with GBM robustly mitigated after surgery compared with that before surgery, further corroborating the signi cant clinical correlation of SPP1 with GBM. Importantly, our study is the rst to assess the expression level of SPP1 in peripheral serum of GBM patient, since preceding studies focused on SPP1expression in glioma cell lines or tissues from surgical resection using IHC and western blot [51]. Furthermore, we discovered that SPP1 had a high diagnostic value in GBM with considerable sensitivity and speci city.…”

Section: Discussionmentioning

confidence: 81%

Secreted Phosphoprotein 1 (SPP1) Promotes Angiogenesis of Glioblastoma Through Up-regulating PSMA Expression Via Transcription Factor HIF-1α

Zheng

et al. 2022

Preprint

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Background: Glioblastoma multiforme (GBM) is a highly vascular-rich and devastatingly aggressive type of malignant brain tumors, thus anti-angiogenesis therapy plays an essential role in the treatment of GBM. Our previous study had showed that the prostate-specific membrane antigen (PSMA) promoted angiogenesis of GBM though interacting with Integrin β4 (ITGB4) and regulating NF-kB signaling pathway. This study aims to explore the upstream molecular mechanism of GBM regulating the expression of PSMA and promoting angiogenesis process.Methods: Human cytokine antibody array and bioinformatics were used to explore potential cytokines involved in regulating PSMA expression. Recombinant protein was applied and Western blot, qRT-PCR were assessed to verify that the contributing cytokine was SPP1. Expression levels, prognosis and receiver operation characteristic (ROC) curve of SPP1 were determined by bioinformatics to evaluate its clinical value. ELISA was conducted to evaluate the variation of SPP1 in the serum of GBM patients pre- and post-surgery. Potential transcription factor mediating the expression of PSMA was sifted through PROMO and JASPAR website. ChIP assay and dual luciferase were used to confirm that the transcription factor regulating PSMA expression was HIF-1α. Cellular migration and tube formation ability were assessed by scratch assay and tube formation assay in human umbilical vein endothelial cells (HUVECs).Results: We demonstrated that cytokine SPP1 secreted from GBM could regulate the expression of PSMA in HUVEC. SPP1 was abundantly expressed in the GBM, and the high expression of SPP1 is associated with poor prognosis. Recombinant protein SPP1 could promote migration and tube formation ability of HUVEC. The mechanistic study revealed that SPP1 regulated the expression of PSMA through transcription factor HIF1α. In addition, knockdown of HIF1α could reduce the expression of PSMA in HUVEC, and block the ability of SPP1 in promoting migration and tube formation of HUVEC. Furthermore, SPP1 and HIF1α both had a high value of clinical diagnosis with considerable sensitivity and specificity.Conclusions: In this study, we identified that upstream cytokine SPP1 secreted from GBM could upregulate PSMA expression in endothelial cells via transcription factor HIF1α, which constructs a positive chain in angiogenesis and provides promising candidates for targeted therapy of GBM.

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“…Eight genes, which were found to be downregulated in treated compared to untreated GBM tissue and are known to be associated with proliferation of neuronal and/or cancer cells, were chosen for further analysis. This analysis revealed a downregulation of SPP1 which has been shown to be overexpressed in grade IV gliomas and which is related to worse overall survival also in patients with lower-grade glioma 42 . Some isoforms of SPP1 are in fact known to promote glioma cell invasion 43 .…”

Section: Discussionmentioning

confidence: 83%

Deep sequencing and automated histochemistry of human tissue slice cultures improve their usability as preclinical model for cancer research

Haehnel

Reiche

Loeffler

et al. 2019

Sci Rep

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Cancer research requires models closely resembling the tumor in the patient. Human tissue cultures can overcome interspecies limitations of animal models or the loss of tissue architecture in in vitro models. However, analysis of tissue slices is often limited to histology. Here, we demonstrate that slices are also suitable for whole transcriptome sequencing and present a method for automated histochemistry of whole slices. Tumor and peritumoral tissue from a patient with glioblastoma was processed to slice cultures, which were treated with standard therapy including temozolomide and X-irradiation. Then, RNA sequencing and automated histochemistry were performed. RNA sequencing was successfully accomplished with a sequencing depth of 243 to 368 x 106 reads per sample. Comparing tumor and peritumoral tissue, we identified 1888 genes significantly downregulated and 2382 genes upregulated in tumor. Treatment significantly downregulated 2017 genes, whereas 1399 genes were upregulated. Pathway analysis revealed changes in the expression profile of treated glioblastoma tissue pointing towards downregulated proliferation. This was confirmed by automated analysis of whole tissue slices stained for Ki67. In conclusion, we demonstrate that RNA sequencing of tissue slices is possible and that histochemical analysis of whole tissue slices can be automated which increases the usability of this preclinical model.

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Identification of Secreted Phosphoprotein 1 (SPP1) as a Prognostic Factor in Lower-Grade Gliomas

Cited by 19 publications

References 65 publications

Expression and prognostic potential of GPX1 in human cancers based on data mining

Expression and prognostic potential of GPX1 in human cancers based on data mining

Secreted Phosphoprotein 1 (SPP1) Promotes Angiogenesis of Glioblastoma Through Up-regulating PSMA Expression Via Transcription Factor HIF-1α

Deep sequencing and automated histochemistry of human tissue slice cultures improve their usability as preclinical model for cancer research

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