Dataset Information

Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma.

ABSTRACT: Objective: To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS). Methods: The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis and Cox regression model were used to identify parameters correlated with progression-free survival (PFS) and overall survival (OS). Results: Compared with the contralateral normal brain region, postoperative PEZ showed a lower ratio of NAA/Cr (1.20 ± 0.42 vs. 1.81 ± 0.48, P < 0.001), and higher ratios of Cho/Cr and Cho/NAA (1.36 ± 0.44 vs. 1.02 ± 0.27, P < 0.001 and 1.32 ± 0.59 vs. 0.57 ± 0.14, P < 0.001). Both the ratios of Cho/NAA and NAA/Cr were identified as prognostic factors in univariate analysis (P < 0.05), while only Cho/NAA ? 1.31 was further confirmed as an independent risk factor for early recurrence in the Cox regression model (P < 0.01). According to the factors of MGMT promoter unmethylation, without radiotherapy and Cho/NAA ? 1.31, a prognostic scoring scale for GBM was established, which could divide patients into low-risk, moderate-risk, and high-risk groups. There was a significant difference of survival rate between the three groups (P < 0.001). Conclusions: Higher Cho/NAA ratio in the postoperative PEZ of GBM predicts earlier recurrence and is associated with poor prognosis. The prognostic scoring scale based on clinical, molecular and metabolic parameters of patients with GBM can help doctors to make more precise prediction of survival time and to adjust therapeutic regimens.

SUBMITTER: Cui Y

PROVIDER: S-EPMC7747764 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma.

Cui Yong Y Zeng Wei W Jiang Haihui H Ren Xiaohui X Lin Song S Fan Yanzhu Y Liu Yapeng Y Zhao Jizong J

Frontiers in neurology 20201204

<b>Objective:</b> To explore the prognostic significance of metabolic parameters in postoperative peritumoral edema zone (PEZ) of patients with glioblastoma (GBM) based on proton magnetic resonance spectroscopy (MRS). <b>Methods:</b> The postoperative MRS data of 67 patients with GBM from Beijing Tiantan Hospital were retrospectively reviewed. Metabolite ratios including Cho/NAA, Cho/Cr, and NAA/Cr in both postoperative PEZ and contralateral normal brain region were recorded. Log-rank analysis a ...[more]

PMID: 33343496

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Project description:BACKGROUND AND PURPOSE:Damage to the blood-brain barrier with subsequent contrast enhancement is a hallmark of glioblastoma. Non-enhancing tumor invasion into the peritumoral edema is, however, not usually visible on conventional magnetic resonance imaging. New quantitative techniques using relaxometry offer additional information about tissue properties. The aim of this study was to evaluate longitudinal relaxation R1, transverse relaxation R2, and proton density in the peritumoral edema in a group of patients with malignant glioma before surgery to assess whether relaxometry can detect changes not visible on conventional images. METHODS:In a prospective study, 24 patients with suspected malignant glioma were examined before surgery. A standard MRI protocol was used with the addition of a quantitative MR method (MAGIC), which measured R1, R2, and proton density. The diagnosis of malignant glioma was confirmed after biopsy/surgery. In 19 patients synthetic MR images were then created from the MAGIC scan, and ROIs were placed in the peritumoral edema to obtain the quantitative values. Dynamic susceptibility contrast perfusion was used to obtain cerebral blood volume (rCBV) data of the peritumoral edema. Voxel-based statistical analysis was performed using a mixed linear model. RESULTS:R1, R2, and rCBV decrease with increasing distance from the contrast-enhancing part of the tumor. There is a significant increase in R1 gradient after contrast agent injection (P < .0001). There is a heterogeneous pattern of relaxation values in the peritumoral edema adjacent to the contrast-enhancing part of the tumor. CONCLUSION:Quantitative analysis with relaxometry of peritumoral edema in malignant gliomas detects tissue changes not visualized on conventional MR images. The finding of decreasing R1 and R2 means shorter relaxation times closer to the tumor, which could reflect tumor invasion into the peritumoral edema. However, these findings need to be validated in the future.

Project description:The present study aimed to identify differentially regulated genes between the peritumoral brain zone (PBZ) and tumor core (TC) of glioblastoma (GBM), to elucidate the underlying molecular mechanisms and provide a target for the treatment of tumors. The GSE13276 and GSE116520 datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) for the PBZ and TC were obtained using the GEO2R tool. The bioinformatics and evolutionary genomics online tool Venn was used to identify common DEGs between the two datasets. The Database for Annotation, Visualization, and Integrated Discovery online tool was used to analyze enriched pathways of the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. The Search Tool for the Retrieval of Interacting Genes/Proteins online tool was used to construct a protein-protein interaction (PPI) network of DEGs. Hub genes were identified using Cytohubba, a plug-in for Cytoscape. The Gene Expression Profiling Interactive Analysis (GEPIA) database was utilized to perform survival analysis. In total, 75 DEGs, including 12 upregulated and 63 downregulated genes, were identified. In the GO term analysis, these DEGs were mainly enriched in 'regulation of angiogenesis' and 'central nervous system development'. Furthermore, in the KEGG pathway analysis, the DEGs were mainly enriched in 'bladder cancer' and 'endocytosis'. When filtering the results of the PPI network analysis using Cytohubba, a total of 10 hub genes, including proteolipid protein 1, myelin associated oligodendrocyte basic protein, contactin 2, myelin oligodendrocyte glycoprotein, myelin basic protein, myelin associated glycoprotein, SRY-box transcription factor 10, C-X-C motif chemokine ligand 8 (CXCL8), vascular endothelial growth factor A (VEGFA) and plasmolipin, were identified. These hub genes were further subjected to GO term and KEGG pathway analysis, and were revealed to be enriched in 'central nervous system development', 'bladder cancer' and 'rheumatoid arthritis'. These hub genes were used to perform survival analysis using the GEPIA database, and it was determined that VEGFA and CXCL8 were significantly associated with a reduction in the overall survival of patients with GBM. In conclusion, the results suggest that the recurrence of GBM is associated with high gene expression levels VEGFA and CXCL8, and the development of the central nervous system.

Project description:BackgroundThis study aimed to investigate the role of the alpha fetoprotein (AFP) ratio before and after curative resection in the prognosis of patients with hepatocellular carcinoma (HCC) and to develop a novel pre- to postoperative AFP ratio nomogram to predict recurrence free survival (RFS) for HCC patients after curative resection.MethodsA total of 485 pathologically confirmed HCC patients who underwent radical hepatectomy from January 2010 to December 2018 were retrospectively analyzed. The independent prognostic factors of hepatocellular carcinoma were identified by multivariate COX proportional model analysis, and the nomogram model was constructed. The receiver operating characteristic and the C-index were used to evaluate the accuracy and efficacy of the model prediction, the correction curve was used to assess the calibration of the prediction model, and decision curve analysis was used to evaluate the clinical application value of the nomogram model.ResultsA total of 485 HCC patients were divided into the training cohort (n = 340) and the validation cohort (n = 145) by random sampling at a ratio of 7:3. Using X-tile software, it was found that the optimal cut-off value of the AFP ratio in the training cohort was 0.8. In both cohorts, the relapse-free survival of patients with an AFP ratio <0.8 (high-risk group) was significantly shorter than in those with an AFP ratio ≥0.8 (low-risk group) (P < 0.05). An AFP ratio <0.8 was an independent risk factor for recurrence of HCC after curative resection. Based on the AFP ratio, BCLC stage and cirrhosis diagnosis, a satisfactory nomogram was developed. The AUC of our nomogram for predicting 1-, 3-, and 5-year RFS was 0.719, 0.690, and 0.708 in the training cohort and 0.721, 0.682, and 0.681 in the validation cohort, respectively. Furthermore, our model demonstrated excellent stratification as well as clinical applicability.ConclusionThe AFP ratio was a reliable biomarker for tumor recurrence. This easy-to-use AFP ratio-based nomogram precisely predicted tumor recurrence in HCC patients after curative resection.

Project description:IntroductionPeritumoral brain edema (PTBE) has been widely reported with many brain tumors, especially with glioma. Since the blood-brain barrier (BBB) is essential for maintaining minimal permeability, any alteration in the interaction of BBB components, specifically in astrocytes and tight junctions (TJ), can result in disrupting the homeostasis of the BBB and making it severely leaky, which subsequently generates edema.ObjectiveThis study aimed to evaluate the functional gliovascular unit of the BBB by examining changes in the expression of claudin (CLDN) genes and the expression of transient receptor potential (TRP) membrane channels, additionally to define the correlation between their expressions. The evaluation was conducted using in vitro spheroid swelling models and tumor samples from glioma patients with PTBE.ResultsThe results of the spheroid model showed that the genes TRPC3, TRPC4, TRPC5, and TRPV1 were upregulated in glioma cells either wild-type isocitrate dehydrogenase 1 (IDH1) or the IDH1 R132H mutant, with or without NaCl treatment. Furthermore, TRP genes appeared to adversely correlate with the up regulation of CLDN1, CLDN3, and CLDN5 genes. Besides, the upregulation of TRPC1 and TRPC4 in IDH1mt-R132H glioma cells. On the other hand, the correlation analysis revealed different correlations between different proteins in PTBE. CLDN1 exhibits a slight positive correlation with CLDN3. Similarly, TRPV1 displays a slight positive correlation with TRPC1. In contrast, TRPC4 shows a slight negative correlation with TRPC5. On the other hand, TRPC3 demonstrates a slight positive correlation with TRPC5, while the non-PTBE analysis highlights a moderate positive correlation between CLDN1 and TRPM4 while CLDN3 exhibits a moderate negative correlation with TRPC4. Additionally, CLDN5 demonstrates a slight negative correlation with TRPC4 but a moderate positive correlation with TRPC3. Furthermore, TRPC1 have a slight negative correlation with TRPV1, TRPC3 exhibiting a slight positive correlation with TRPC4, and TRPV1 showing a slight negative correlation with TRPC5.ConclusionAs a conclusion, the current study provided evidence of a slight negative correlation between TRPs and CLDN gene expression in PTBE patients and confirmatory results with some of the genes in cell model of edema.

Project description:Adult diffuse gliomas commonly recur regardless of therapy. As recurrence typically arises from the peritumoral edema adjacent to the resected bulk tumor, the profiling of somatic mutations from infiltrative malignant cells within this critical, unresected region could provide important insights into residual disease. A key obstacle has been the inability to distinguish between next-generation sequencing (NGS) noise and the true but weak signal from tumor cells hidden among the noncancerous brain tissue of the peritumoral edema. Here, we developed and validated True2 sequencing to reduce NGS-associated errors to <1 false positive/100 kb panel positions while detecting 97.6% of somatic mutations with an allele frequency ≥0.1%. True2 was then used to study the tumor and peritumoral edema of 22 adult diffuse gliomas including glioblastoma, astrocytoma, oligodendroglioma, and NF1-related low-grade neuroglioma. The tumor and peritumoral edema displayed a similar mutation burden, indicating that surgery debulks these cancers physically but not molecularly. Moreover, variants in the peritumoral edema included unique cancer driver mutations absent in the bulk tumor. Finally, analysis of multiple samples from each patient revealed multiple subclones with unique mutations in the same gene in 17 of 22 patients, supporting the occurrence of convergent evolution in response to patient-specific selective pressures in the tumor microenvironment that may form the molecular foundation of recurrent disease. Collectively, True2 enables the detection of ultralow frequency mutations during molecular analyses of adult diffuse gliomas, which is necessary to understand cancer evolution, recurrence, and individual response to therapy.SignificanceTrue2 is a next-generation sequencing workflow that facilitates unbiased discovery of somatic mutations across the full range of variant allele frequencies, which could help identify residual disease vulnerabilities for targeted adjuvant therapies.

Dataset Information

Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma.

Publications

Higher Cho/NAA Ratio in Postoperative Peritumoral Edema Zone Is Associated With Earlier Recurrence of Glioblastoma.

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