The investigation of changes in proteins expression (Apolipoprotein A1 and albumin) in malignant astrocytoma brain tumor

Hashemi, Mehrdad; Pooladi, Mehdi; Abad, Solmaz Khaghani Razi

doi:10.4103/0973-1482.131413

Cited by 13 publications

(7 citation statements)

References 34 publications

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“…Our discovery dataset and literature also pointed at upregulation of several apolipoproteins in gliomas and meningiomas (12,31,32). APOE plays a vital role in redistribution of intracellular lipid and tissue reconstruction in CNS through a receptor dependent pathway.…”

Section: Discussionsupporting

confidence: 61%

Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors

et al. 2021

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The emergence of omics technologies over the last decade has helped in advancement of research and our understanding of complex diseases like brain cancers. However, barring genomics, no other omics technology has been able to find utility in clinical settings. The recent advancements in mass spectrometry instrumentation have resulted in proteomics technologies becoming more sensitive and reliable. Targeted proteomics, a relatively new branch of mass spectrometry-based proteomics has shown immense potential in addressing the shortcomings of the standard molecular biology-based techniques like Western blotting and Immunohistochemistry. In this study we demonstrate the utility of Multiple reaction monitoring (MRM), a targeted proteomics approach, in quantifying peptides from proteins like Apolipoprotein A1 (APOA1), Apolipoprotein E (APOE), Prostaglandin H2 D-Isomerase (PTGDS), Vitronectin (VTN) and Complement C3 (C3) in cerebrospinal fluid (CSF) collected from Glioma and Meningioma patients. Additionally, we also report transitions for peptides from proteins – Vimentin (VIM), Cystatin-C (CST3) and Clusterin (CLU) in surgically resected Meningioma tissues; Annexin A1 (ANXA1), Superoxide dismutase (SOD2) and VIM in surgically resected Glioma tissues; and Microtubule associated protein-2 (MAP-2), Splicing factor 3B subunit 2 (SF3B2) and VIM in surgically resected Medulloblastoma tissues. To our knowledge, this is the first study reporting the use of MRM to validate proteins from three types of brain malignancies and two different bio-specimens. Future studies involving a large cohort of samples aimed at accurately detecting and quantifying peptides of proteins with roles in brain malignancies could potentially result in a panel of proteins showing ability to classify and grade tumors. Successful application of these techniques could ultimately offer alternative strategies with increased accuracy, sensitivity and lower turnaround time making them translatable to the clinics.

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Section: Discussionsupporting

confidence: 61%

Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors

et al. 2021

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“…Therapies targeting neovascularization in malignant gliomas show promise in improving outcome[ 4 , 5 ]. Microvessel density (MVD) has been used to predict treatment outcome[ 6 , 7 ]. It has been reported that increased CD105-MVD correlates with shorter survival[ 8 ].…”

Section: Introductionmentioning

confidence: 99%

CT Perfusion with Acetazolamide Challenge in C6 Gliomas and Angiogenesis

Feng

et al. 2015

PLoS ONE

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BackgroundThis study was performed to investigate the correlation between CT perfusion with acetazolamide challenge and angiogenesis in C6 gliomas.MethodsThirty-two male Sprague-Dawley rats were evaluated. The rats were divided randomly to four groups: eight rats with orthotopically implanted C6 gliomas at 10-days old (Group A), eight rats with gliomas at 14-days old (Group B), eight rats with gliomas at 18-days old (Group C), eight rats with orthotopically injected normal saline served as controls. CT perfusion was performed before and after administration of acetazolamide. Changes in perfusion parameters due to acetazolamide administration were calculated and analyzed.ResultsElevated carbon dioxide partial pressure and decreased pH were found in all 32 rats post acetazolamide challenge (P<0.01). Cerebral blood flowpre-challenge was increased in group C (95.0±2.5 ml/100g/min), as compared to group B (80.1±11.3 ml/100g/min) and group A (63.1±2.1 ml/100g/min). Cerebral blood flow percentage changes were detected with a reduction in group C (54.2±4.8%) as compared to controls (111.3±22.2%). Cerebral blood volume pre-challenge was increased in group C (50.8±1.7ml/100g), as compared to group B (45.7±1.9 ml/100g) and group A (38.2±0.8 ml/100g). Cerebral blood volume percentage changes were decreased in group C (23.5±4.6%) as compared to controls (113.5±30.4%). Angiogenesis ratio = [(CD105-MVD) / (FVIII-MVD)] ×100%. Positive correlations were observed between CD105-microvessel density, angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flowpre-challenge, cerebral blood volume pre-challenge. Negative correlations were observed between CD105-microvessel density and cerebral blood flow percentage changes (P<0.01, correlation coefficient r=-0.788), cerebral blood volume percentage changes (P<0.01, r=-0.703). Negative correlations were observed between angiogenesis ratio, vascular endothelial growth factor, proliferation marker and cerebral blood flow percentage changes, cerebral blood volume percentage changes.ConclusionOur findings suggest that CT perfusion with challenge can provide new insight into non-invasive assessment of rat C6 glioma angiogenesis.

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“…42 , 43 Moreover, Chimienti et al 44 reported that APOA inhibited the secretion of IL-6 by interfering with lipopolysaccharide signaling in a human astrocytoma cell line. Hashemi et al 45 discovered that APOA1 was a key oncogene in malignant astrocytoma tumors due to its functional consequences in tumor growth, angiogenesis and migration. As described previously, APOB is mainly responsible for the transportation of lipids, and methylation of APOB leads to the accumulation of extracellular lipids.…”

Section: Discussionmentioning

confidence: 99%

<p>Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma</p>

Han

Chen

et al. 2020

OTT

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Background: This study was performed to explore the clinical and prognostic significance of APOB mRNA expression, DNA methylation and APOB mutation in patients with lowgrade glioma (LGG). Methods: Bioinformatic analysis was conducted using genomic, clinical and survival data from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Serum APOB protein levels were measured via immunoturbidimetry in 150 patients with LGG and 100 healthy controls from Hubei General Hospital. Results: There was a negative association between the levels of APOB mRNA and DNA methylation (r=−0.355, P<0.0001) in patients with LGG from the TCGA database. Additionally, LGG patients with low levels of APOB mRNA exhibited better overall survival (OS) than those with high levels of APOB mRNA (HR=0.637, P=0.0085). The survival time of LGG patients with APOB hypermethylation was markedly longer than that of patients with APOB hypomethylation (HR=0.423, P=0.0185). The prognostic significance of APOB mRNA and DNA methylation was also validated with the CGGA cohort, and a similar conclusion was reached. APOB gene mutations were observed in 3% of patients with LGG from the TCGA database, and no association was detected between APOB mutations and OS (P=0.164). Furthermore, the levels of APOB protein were much lower in patients with LGG than in normal individuals (P=0.0022), and the expression of APOB protein was markedly different among groups when stratified by histological type (P<0.0001) and histological-molecular classification (P<0.0001). Conclusion: APOB mRNA expression is negatively regulated by DNA methylation in patients with LGG. Low expression or hypermethylation of APOB might predict relatively favorable survival in patients with LGG.

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The investigation of changes in proteins expression (Apolipoprotein A1 and albumin) in malignant astrocytoma brain tumor

Abstract: The vascular microenvironment of glioma play a major role in determining the pathophysiological character is tics of the tumor. apo A1 and albumin are very significant due to their functional consequences in glioma tumor growth, migration and angiogenesis.

Cited by 13 publications

References 34 publications

Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors

Multiple Reaction Monitoring-Based Targeted Assays for the Validation of Protein Biomarkers in Brain Tumors

CT Perfusion with Acetazolamide Challenge in C6 Gliomas and Angiogenesis

<p>Low Expression of APOB mRNA or Its Hypermethylation Predicts Favorable Overall Survival in Patients with Low-Grade Glioma</p>

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