Dataset Information

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors.

ABSTRACT: The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease recognition. Glycosylation is a chemical modification of proteins, reportedly altered in several inflammatory and malignant diseases, providing a potential alternative route for disease detection. In this paper, we report the quantitative analysis of serum N-glycosylation of patients diagnosed with primary and metastatic brain tumors. PNGase-F-digested and procainamide-labeled serum glycans were purified by magnetic nanoparticles, followed by quantitative liquid chromatographic analysis. The glycan structures were identified by the combination of single quad mass spectrometric detection and exoglycosidase digestions. Linear discriminant analysis provided a clear separation of different disease groups and healthy controls based on their N-glycome pattern. Altered distribution of biantennary neutral, sialylated but nonfucosylated, and sialylated-fucosylated structures were found to be the most significant changes. Our results demonstrate that serum glycosylation monitoring could improve the detection of malignancy.

SUBMITTER: Varadi C

PROVIDER: S-EPMC7825111 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors.

Váradi Csaba C Hajdu Viktória V Farkas Flóra F Gilányi Ibolya I Oláh Csaba C Viskolcz Béla B

Life (Basel, Switzerland) 20210106 1

The identification of patients with different brain tumors is solely built on imaging diagnostics, indicating the need for novel methods to facilitate disease recognition. Glycosylation is a chemical modification of proteins, reportedly altered in several inflammatory and malignant diseases, providing a potential alternative route for disease detection. In this paper, we report the quantitative analysis of serum N-glycosylation of patients diagnosed with primary and metastatic brain tumors. PNGa ...[more]

PMID: 33418875

Similar Datasets

Project description:Background: Surgery has been the primary treatment in patients with localized gastrointestinal stromal tumors (GISTs) for many decades, whereas it remains controversial regarding the efficacy of primary tumor resection for metastatic GISTs treated with chemotherapy, and likewise it is unclear who would benefit from the surgical resection. Methods: GISTs patients with distant metastases were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. Cox proportional hazards regression models were used to identify prognostic factors of overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analyses and log-rank tests were conducted to assess the effectiveness of surgery on survival. Results: In total, of 455 patients with metastatic GISTs, 235 patients (51.6%) underwent primary tumor resection and 220 patients (48.4%) did not. Median survival of patients in resection group was 72 (95% CI: 62.90-81.10) months vs. 40 (95% CI: 29.53-50.47) months for those in non-resection group (p < 0.001). Similarly, surgery in conjunction with chemotherapy led to a favorable impact on survival than chemotherapy alone (OS: 72 vs. 40 months, p < 0.001; CSS: 74 vs. 44 months, p < 0.001). Multivariable analysis showed that both OS (HR: 0.581, 95% CI: 0.386-0.874, p = 0.009) and CSS (HR: 0.663, 95% CI: 0.439-0.912, p = 0.042] were dramatically improved in patients with surgical removal of primary site, as well as primary tumor size between 5 and 10 cm, while increasing age was predictive of poorer survival. Stratified analysis revealed that patients with tumor locations in the stomach demonstrated a prolonged survival after surgery, with no significant differential surgical effect between the stomach and small intestine. Conclusions: Our study preliminarily suggests that carefully selected patients with metastatic GISTs might prolong survival after treatment of surgery, especially those with a primary tumor between 5 and 10 cm and a tumor located in the stomach.

Project description:PurposeThere is a continuous search for imaging techniques with high sensitivity and specificity for brain tumors. Positron emission tomography (PET) imaging has shown promise, though many PET agents either have a low tumor specificity or impractical physical half-lives. [124I]CLR1404 is a small molecule alkylphosphocholine analogue that is thought to bind to plasma membrane lipid rafts and has shown high tumor-to-background ratios (TBR) in a previous pilot study in brain tumor patients. This study attempts to define the clinical value of [124I]CLR1404 PET/CT (aka CLR124).ProceduresAdult patients with new or suspected recurrence of high-grade primary or metastatic brain tumors (N = 27) were injected with [124I]CLR1404 followed by PET/CT at 6, 24, and 48 h. Standard uptake values (SUV) and TBR values were calculated for all time points. Uptake of [124I]CLR1404 was qualitatively assessed, compared with magnetic resonance imaging (MRI), and correlated with clinical outcome. Final diagnosis (N = 25) was established based on surgically resected tissue or long-term follow-up.ResultsPositive uptake with high TBR was detected in all but one patient with a final diagnosis of primary/recurrent brain tumor (12/13) and in less than half of patients with treatment-related changes (5/12). Concordance between [124I]CLR1404 uptake and contrast enhancement on MRI was seen in < 40 %, with no concordance between T2-hyperintensities and uptake. No significant difference in overall outcome was found between patients with and without [124I]CLR1404 uptake.ConclusionsThe uptake pattern in these patients suggests a very high sensitivity of [124I]CLR1404 PET/CT for diagnosing tumor tissue; however, tumor specificity needs to be further defined. Relative lack of concordance with standard MRI characteristics suggests that [124I]CLR1404 PET/CT provides additional information about brain tumors compared to MRI alone, potentially improving clinical decision-making.

Project description:BackgroundBreast cancer brain metastases (BrMs) are defined by complex adaptations to both adjuvant treatment regimens and the brain microenvironment. Consequences of these alterations remain poorly understood, as does their potential for clinical targeting. We utilized genome-wide molecular profiling to identify therapeutic targets acquired in metastatic disease.MethodsGene expression profiling of 21 patient-matched primary breast tumors and their associated brain metastases was performed by TrueSeq RNA-sequencing to determine clinically actionable BrM target genes. Identified targets were functionally validated using small molecule inhibitors in a cohort of resected BrM ex vivo explants (n = 4) and in a patient-derived xenograft (PDX) model of BrM. All statistical tests were two-sided.ResultsConsiderable shifts in breast cancer cell-specific gene expression profiles were observed (1314 genes upregulated in BrM; 1702 genes downregulated in BrM; DESeq; fold change > 1.5, Padj < .05). Subsequent bioinformatic analysis for readily druggable targets revealed recurrent gains in RET expression and human epidermal growth factor receptor 2 (HER2) signaling. Small molecule inhibition of RET and HER2 in ex vivo patient BrM models (n = 4) resulted in statistically significantly reduced proliferation (P < .001 in four of four models). Furthermore, RET and HER2 inhibition in a PDX model of BrM led to a statistically significant antitumor response vs control (n = 4, % tumor growth inhibition [mean difference; SD], anti-RET = 86.3% [1176; 258.3], P < .001; anti-HER2 = 91.2% [1114; 257.9], P < .01).ConclusionsRNA-seq profiling of longitudinally collected specimens uncovered recurrent gene expression acquisitions in metastatic tumors, distinct from matched primary tumors. Critically, we identify aberrations in key oncogenic pathways and provide functional evidence for their suitability as therapeutic targets. Altogether, this study establishes recurrent, acquired vulnerabilities in BrM that warrant immediate clinical investigation and suggests paired specimen expression profiling as a compelling and underutilized strategy to identify targetable dependencies in advanced cancers.

Dataset Information

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors.

Publications

The Analysis of Human Serum N-Glycosylation in Patients with Primary and Metastatic Brain Tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets