bluuebunny/crossref_metadata_2025_split huggingface dataset:
BIOM-25. IDENTIFICATION OF PLASMA-DERIVED PREDICTIVE BIOMARKERS INCLUDING SERPINA3 FOR GLIOMA AND GLIOBLASTOMA
Authors: Etter Manina , Duchemin Wandrille , Shekarian Tala , Durano Célia , Vogel Julian , Ritz Marie-Françoise , Hutter Gregor 
Published: November 2023

Abstract
Advancement in the diagnosis and surveillance of gliomas has been limited posing both diagnostic and therapeutic challenges. Definitive diagnosis, distinction of progression versus pseudoprogression and prognosis assessment still depend on invasive neurosurgical biopsy procedure. Minimally-invasive plasma sampling could minimize the risks associated with invasive tissue sampling. Therefore, we aimed to identify specific plasma protein patterns of low- and high-grade glioma patients, compared to healthy individuals and investigated whether different plasma-derived protein signatures were associated with survival in glioma patients. Plasma samples were from patients with glioma grades I to IV collected during tumor removal and from healthy controls donating blood were processed for Liquid Chromatography Mass Spectrometry (LC/MS) proteomics after depletion of the 14 most abundant plasma proteins, in order to specifically detect low-abundant tumor-derived proteins. Overall, 646 proteins were measured across 104 plasma samples from glioma patients and 57 plasmas from the healthy cohort. PCA showed 2 clusters of samples, one containing low- and high-grade glioma samples and the other containing healthy and some grade IV (GBM) plasma samples. Interestingly, a spatial analysis of tumor location by MRI associated the GBM samples separated from healthy samples with subventricular vicinity. 26 differentially expressed proteins (DEPs) were identified discriminating between glioma and healthy samples and 30 DEPs discriminating GBM and healthy samples. The top most overexpressed proteins in gliomas vs controls were SERPINA3, F13A1, and TKT. Multivariate analysis identified SERPINA3, PPBP and MYH9 as strong discriminators of healthy vs GBM but also of low-grade vs GBM, indicating that these proteins may represent specific plasma biomarkers for GBM. SERPINA3, MYL1 and CLU were associated with poor survival in GBM. In conclusion, we describe sets of plasma derived proteins, in particular SERPINA3, as predictive biomarkers that could be used to assess tumor progression allowing patient-centered treatment options.
BIOM-29. FIBRONECTIN TYPE III DOMAIN CONTAINING 3B AS PROGNOSTIC BIOMARKER AND REGULATORY TARGET FOR MALIGNANT BRAIN TUMOR
Authors: Kwon Hyukjun , Yun Minji , Bang Minji , Lee Jungsul , Ko Hae Young , Chong Kyuha 
Published: November 2023

Abstract
Malignant brain tumor (MBT) is an aggressive tumor with high drug-resistance and recurrence rates. Using ‘Oncopression’ big data analysis, we found that a fibronectin-related protein, fibronectin type III domain containing 3B (FNDC3B), was specifically overexpressed in brain tumor patients and conducted a pilot and mechanism study on the role of FNDC3B in MBT. We evaluated the functional significance of FNDC3B in MBT using FNDC3B specific siRNA and performing cell viability assay, real-time qPCR, Western blot, 3D-invasion assay, and wound healing assay. Furthermore, using proteome profiler human phospho-kinase arrays, we investigated the correlated signaling which activated while FNDC3B-mediated MBT cell progression. We found that down-regulation of FNDC3B decreased tumor cell proliferation, migratory and invasiveness properties as well as stemness phenotype which are hallmarks of cancer progression. Furthermore, we demonstrate that PI3K/AKT signaling pathways were involved mainly in FNDC3B-related tumor growth and mesenchymal phenotypes. Although follow-up studies are necessary, the results of this study suggest that FNDC3B is worth investigating as a novel alternative diagnostic and therapeutic target candidate for MBT.
BIOM-36. PREOPERATIVE IMMUNE AND INFLAMMATORY FACTORS IN PERIPHERAL BLOOD PREDICT PROGNOSIS OF GLIOMA AND CORRELATE WITH GRADES AND SUBTYPES: A PROSPECTIVE MULTI-INSTITUTIONAL STUDY OF 1282 PATIENTS
Authors: Zhong Sheng , Yang Wenzhuo , Zhang Zhiyun , Xie Haoqun , Sai Ke , Mou Yonggao 
Published: November 2023

Abstract

BACKGROUND
Peripheral blood immune and inflammatory factors can reflect glioma patients' immune status and inform anti-tumor immunotherapy, but research in this field is limited compared to tumor microenvironment studies. We aim to investigate the relationship between these circulating factors and glioma grades, subtypes, and prognosis.

METHODS
From October 2006 to April 2022, 1282 patients with primary gliomas were enrolled in this study, and their preoperative peripheral blood was collected. Correlations between immune and inflammatory factors and different glioma grades and subtypes were analyzed using ANOVA, t-test, and Ordinal Logistic Regression. ROC curve analysis was used to evaluate the diagnostic efficiency of these factors. In addition, the Cox regression model, K-M survival analysis, and other methods were used to study the relationship between these factors and the prognosis and survival of patients.

RESULTS
The results showed that with the higher clinical grade, the percentage of NK cells in peripheral blood increases while the percentage of Th and T lymphocytes decreases. C4 levels and percentage of B lymphocytes were higher in grade I gliomas than in other grades. The percentage of NK and Th cells also correlated with glioma subtypes. Immunoglobulin light chains were associated with a favorable prognosis, whereas a higher percentage of peripheral B lymphocytes in grade IV patients was associated with a poor prognosis.

CONCLUSIONS
The relationship between immune and inflammatory factors and the grades and subtypes of glioma can offer potential opportunities to intervene in these factors that could improve the prognosis of glioma patients. Additionally, it may be helpful to screen glioma and anti-tumor immunotherapy.
BIOM-50. EXOSOMAL MICRORNA EXPRESSION SIGNATURE IN BLOOD AND CEREBROSPINAL FLUID OF GLIOBLASTOMA PATIENTS
Authors: Yamashita Daisuke , Suehiro Satoshi , Nishikawa Masahiro , Inoue Akihiro , Kunieda Takeharu 
Published: November 2023

Abstract
Analysis of exosomes derived from plasma or cerebrospinal fluid (CSF) has emerged as a promising biomarker platform for therapeutic monitoring in glioblastoma patients. However, the contents of the various subpopulations of exosomes in these clinical specimens remain poorly defined. Here we characterize the relative abundance of miRNA species in exosomes derived from the plasma and CSF of glioblastoma patients. To this end, we first employed miRNA arrays to measure the expression of exosomal miRNAs in the plasma from glioblastoma patients (n = 24) and healthy volunteers (n = 7) as control. In addition, we performed global miRNA profiling of exosomal miRNAs in the CSF from glioblastoma patients (n = 5) and non-tumoral patients (n = 3; hydrocephalus patients) as control. In plasma derived exosomes, 80 miRNAs were altered by &gt;2-fold in glioblastoma patients compared to controls. In CSF, 92 miRNAs were altered by &gt;2-fold in glioblastoma patients compared to controls. Combined analysis of plasma and CSF revealed a similar fold difference in eight miRNAs. Next, we measured these eight miRNAs expression in in the plasma from pre- and post-operative glioblastoma patients (n = 9). Among these eight miRNAs, we identified only one miRNA (miR-34b-3p) that was upregulated in exosomes from pre-operative glioblastoma patients. Our results suggest that miR-34b-3p might have a potential as a novel diagnostic marker or a therapeutic tool for glioblastoma patients.
BIOM-54. VALIDATING MCM2 IMMUNOHISTOCHEMISTRY AS A SURROGATE MARKER FOR AGGRESSIVE MENINGIOMA
Authors: Shelbourn Allison , Nuechterlein Nicholas , Parada Carolina Da Silva , Eaton Jessica , Tucker Mallory , Ferreira Manuel , Cimino Patrick 
Published: November 2023

Abstract
Increasing efforts have focused to improve meningioma classification through various multi-omic analyses. One such recent study (Nassiri, et al, Nature, 2021) proposed an integrative molecular classification for meningiomas that included 4 molecular subtypes (MG1-4), with possible immunohistochemical surrogates for each subtype including S100B, ACADL, SCGN, and MCM2, respectively. While these immunohistochemical surrogates have been proposed for meningioma risk-stratification, their clinical utility has not been thoroughly tested. In this study, we sought to evaluate the utility of these immunohistochemical markers for risk-stratification in an independent cohort of meningioma. Tissue microarrays containing meningioma tissues were constructed, immunohistochemically stained, and blindly scored. Our cohort included n = 142 tumors (CNS WHO: 1=93, 2=45, 3=4). Median age was 49 years (range 14-80 years) with 89 female and 53 male patients. We found that MCM2 immunopositivity was a univariate marker of poor prognosis (median progression-free survival 1.2 years) when compared to negative tumors (median progression-free survival 13.0 years). The other three markers (S100B, ACADL, SCGN) were not associated with survival. MCM2 staining held up as a significantly independent (p = 0.03) poor prognostic marker on multivariate Cox proportional hazard modeling including other histopathological features: CNS WHO grade, brain invasion, mitotic index, and tumor size. Although MCM2 staining was independent of CNS WHO grade, all 4 of the CNS WHO 3 meningiomas were positive for MCM2. MCM2-positive tumors had a higher average mitotic count (6.1 mitoses/10hpf) compared to MCM2-negative tumors (1.8 mitoses/10hpf) (p = 0.0002, two-tailed t test). There was no difference between MCM2-positive and MCM2-negative meningiomas in relation to maximum tumor size (4.9cm and 4.2cm, respectively) and mean age (51.71 years and 50.34 years, respectively). In summary, in our cohort we found MCM2 immunopositive staining (surrogate marker for high-risk molecular subtype M4) to be an independently poor prognostic biomarker in meningioma when accounting for other well-established histopathological characteristics.
BIOM-56. THE PRIVATE AND RECURRING ANTIGENIC PROFILE OF MOST AGGRESIVE PEDIATRIC BRAIN TUMORS
Authors: Yang Changlin , Trivedi Vrunda , Yegorov Oleg , Mitchell Duane 
Published: November 2023

Abstract

BACKGROUND
Efficient immunotherapies for pediatric brain tumors face a significant challenge in identifying tumor rejection antigens. To overcome this hurdle, we utilized a comprehensive computer algorithm called the Open Reading Frame Antigen Network (O.R.A.N.).

METHODS
Our focus was on expressed epitopes, including single nucleotide variations, small indels, gene fusions, novel junctions from alternative splicing, and Tumor Associated Antigens (TAAs), for antigenic epitope predictions. To ensure uniqueness, we compared immunogenic TAA epitopes against a personalized human proteomic library, ensuring they were not shared by other expressed isoforms or genes. The immunological landscape of medulloblastoma (n = 170) and DIPG (n = 30) was explored using immune deconvolution techniques combined with single-cell RNA sequencing integration.

RESULTS
Our hypothesis was that medulloblastomas and DIPG exhibit diverse immune profiles and express genes that are rarely found in normal tissues, making them potential targets for immunotherapy. In this study, we found that most neoantigens identified in medulloblastoma patients were unique to each individual, emphasizing the need for personalized neoantigen-based therapies. Interestingly, recurring neoantigens were predominantly present in the MB SHH subgroup, while they constituted only a small fraction of putative antigens in WNT, Group 3, and Group 4 patients. On the other hand, recurring Tumor Associated Antigens (TAAs) were more frequently expressed in the latter three molecular subgroups but not in the SHH subgroup. Thus, a combination of personalized neoantigen vaccines and targeting recurring TAAs could potentially maximize the anti-tumor effects.

CONCLUSION
Medulloblastoma is a disease characterized by its heterogeneity, and current standard treatments do not adequately address this aspect. In the case of DIPG, surgical resection is not a viable option due to its diffuse and infiltrative nature within the brainstem. By leveraging the power of the immune system, cellular immunotherapy holds promise in providing more targeted and personalized treatment options for pediatric brain tumor patients.
BIOS-05. USING DATA-DRIVEN ANALYTICS TO PREDICT SURVIVAL IN PEDIATRIC PATIENTS WITH MEDULLOBLASTOMA: THE UTILITY OF MACHINE LEARNING IN NEXT-GENERATION NEURO-ONCOLOGY PROGNOSTICATION
Authors: Brown Nolan , Kuo Cathleen , Gendreau Julian 
Published: November 2023

Abstract
Medulloblastoma is the most common malignant intracranial tumor affecting the pediatric population. Despite advancements in multimodal treatment over the past 2 decades yielding a &gt;75% 5-year survival rate, children who survive often have substantial neurological and cognitive sequelae. We aimed to identify risk factors and develop a clinically friendly online calculator for prognostic estimation in pediatric medulloblastoma patients. Pediatric patients with a histopathologically confirmed diagnosis of medulloblastoma were extracted from the Surveillance Epidemiology and End RESULTS: database (2000-2019) and split into training and validation cohorts in an 80:20 ratio (Figure 1). The Cox proportional hazards model was used to identify the univariate and multivariate survival predictors. Subsequently, a calculator with those factors was developed to predict 2-, 5-, and 10-year overall survival as well as median survival months for pediatric medulloblastoma patients. The performance of the calculator was determined by discrimination, calibration, and decision curve analysis (DCA). A total of 1,739 pediatric patients with medulloblastoma met the prespecified inclusion criteria. Fourteen variables, including age, sex, race, ethnicity, median household income, county attribute, laterality, histology, anatomical location, tumor grade, tumor size, surgery status, radiotherapy, and chemotherapy, were included in the calculator (). The concordance index was 0.757 in the training cohort and 0.762 in the validation cohort, denoting clinically useful predictive accuracy. Good agreement between the predicted and observed outcomes was demonstrated by the calibration plots. The DCA curves indicated that the developed model has a good clinical prognostic benefit for pediatric medulloblastoma patients, and could aid prognostication efforts in the clinical setting. An easy-to-use prognostic calculator for a large cohort of pediatric patients with medulloblastoma was established. Future efforts should focus on improving granularity of population-based registries and externally validating the proposed calculator.
BIOS-07. SURVIVAL TIME OF GLIOBLASTOMA PATIENTS ENROLLED IN RANDOMIZED CONTROLLED TRIALS: A NEXT GENERATION META-ANALYSIS OF SURVIVAL CURVES
Authors: Hameed Farrukh , Sajjad Omar , Sathyamurthi Sam , Priyadarshini Mamindla , Klaichart Katamon , Thompson Aaliyah , Hegde Tanvi , Wang Yan , Zinn Pascal 
Published: November 2023

Abstract

INTRODUCTION
Glioblastoma is the most common primary malignant brain tumor and remains an incurable disease with high mortality. Randomized controlled trials (RCTs) have investigated novel therapies that have shown promise, but there have been no major additions in the treatment armamentarium in almost two decades.

OBJECTIVE
In a first study of its kind, we investigate the cumulative change in survival times over years for GBM patients by combining the survival outcome data published by multiple trials.

METHODS
A systematic database search of PubMed for GBM RCTs with significant outcomes published after 2005 was conducted. All Kaplan-Meier (KM) survival curves were analyzed. Individual patient data was extracted from the survival curves and a cumulative survival curve was generated with corresponding times calculated. The primary outcome for all included RCT was mortality at longest follow-up.

RESULTS
We identified 14 RCT which contained KM curves presenting sufficient data for individual patient survival data extraction. Survival data of a total of 2294 patients was extracted with 1396 (60.85%) patients in the treatment arms and 898 in the control arms (39.15%). Patients in the control arm received the standard care of GBM management, whereas those in the treatment arms received differing experimental regimens. After generating the cumulative survival curve, the median survival time for patients in the treatment arm was found to be 15.2 months and 11.2 months for the control arm (P &lt; 0.0001). The two-year survival rate was 31.0% for the treatment arm and 15.6% for the control arm.

CONCLUSION
The survival times observed in GBM patients receiving the standard care of management were worse than anticipated. In general, however, overall estimates of survival among patients with GBM have improved with more patients surviving to 2 years.
CNSC-15. MITOCHONDRIA TRANSFER VIA GLIOMA-ASTROCYTE NETWORK MICROTUBES REPROGRAMS TUMOR CELLS FOR ENHANCED TUMORIGENICITY
Authors: Watson Dionysios , Bayik Defne , Storevik Simon , Moreino Shannon , Sprowls Samuel , Han Jianhua , Augustsson Mina , Lauko Adam , Palavalasa Sravya , Rosland Gro , Troike Katie , Tronstad Karl , Wang Sabrina , Sarnow Katharina , Kay Kristen , Lunavat Taral , Silver Daniel , Dayal Sahil , Joseph Justin , Mulkearns-Hubert Erin , Ystaas Lars , Deshpande Gauravi , Guyon Joris , Zhou Yadi , Magaut Capucine , Seder Juliana , Neises Laura , Williford Sarah , Meiser Johannes , Scott Andrew J , Sajjakulnukit Peter , Mears Jason , Bjerkvig Rolf , Chakraborty Abhishek , Daubon Thomas , Cheng Feixiong , Iavarone Antonio , Lyssiotis Costas , Wahl Daniel , Hjelmeland Anita , Hossain Jubayer , Miletic Hrvoje , Lathia Justin 
Published: November 2023

Abstract
Glioblastoma (GBM) interaction with neural cells is critical to its pathobiology. Emerging evidence suggests that GBM cells form an interconnected network with astrocytes, facilitating tumor persistence. Given reports of intercellular transfer of mitochondria in ischemic stroke and other pathologic disease states outside the CNS, we hypothesized that this network facilitates mitochondria transfer from astrocytes to GBM with protumorigenic sequelae. Employing transgenic mice and intracranial viral vector transductions in rats, we found that mitochondria transfer from the TME to GBM occurs in intracranial mouse and patient-derived xenograft models (in nude rats) of GBM. Mitochondria transfer from bone marrow-derived immune cells was minimal in bone marrow chimera mouse models of orthotopic GBM, suggesting that neural cells were the primary mitochondria donors. We confirmed this in vitro, where mouse astrocytes were the major mitochondria donors, followed by microglia and to a much smaller extent bone marrow-derived macrophages. Immortalized human astrocytes transduced with mitochondria-localized mCherry (mito-mCherry) also transferred their mitochondria to numerous patient-derived glioma stem cell (GSC) models at rates of ~5-20%, assessed by flow cytometry and confocal microscopy. Mitochondria were visualized along intercellular actin bridges, structurally resembling tumor microtubes. Blocking actin polymerization or knocking down GAP43 (previously linked to microtube formation) decreased mitochondria transfer from astrocytes to GBM in vitro. Functionally, sorted mito-mCherry+ patient-derived GSCs displayed higher mitochondrial respiration, metabolomic reprogramming and proliferation-promoting phospho-signaling. Mito-mCherry+ GBM cells were more likely to be in the proliferative G2/M phases of the cell cycle, and when sorted from co-cultures had high self-renewal (in vitro) and tumor-initiating capacity (in vivo xenograft mouse model). In ongoing work, we are investigating the role of retrograde GBM to astrocyte transfer of mitochondria by dual-color labeling of the organelle, as well as further delineating the protein machinery involved in this fundamental protumorigenic process, with the goal of identifying novel therapeutic targets.
CNSC-22. CANCER NEUROSCIENCE IN THE OR: ELECTROPHYSIOLOGIC INSIGHTS AT THE TIME OF BRAIN TUMOR RESECTION
Authors: Nelson Thomas , Coughlin Brian , Cahill Daniel , Dunn Gavin , Nahed Brian V , Cosgrove G Rees , Yang Jimmy , Farnsworth Hannah , Richardson R Mark , Cash Sydney , Venkatesh Humsa , Paulk Angelique 
Published: November 2023

Abstract
Pioneering works by Venkatesh and Venkataramani demonstrated that formation of functional neural-glial synapses fosters development and growth of glial neoplasms. Resultant peritumoral neural hyperexcitability associates with tumor progression, though limited in vivo human data have been evaluated to date. We sought to enrich our understanding of these mechanisms by obtaining thin film intraoperative micro-electrocorticography (µECoG) recordings from patients undergoing primary brain tumor resection. METHODS: Intraoperative µECoG data for 8 patients with low- (LGG) and high-grade glioma (HGG, WHO grades 3 and 4) of various tumor histology were included. Analyses excluded any operative behavioral or cognitive tasks and evaluated data prior to stimulation for language or motor mapping. Following low pass (&lt; 200 Hz) and notch filtering at 60, 120, and 180 Hz for ambient electrical noise, bandpower was calculated using multitaper spectral analysis for low frequency (LF, &lt; 1 Hz), delta (1-4 Hz), beta (12-30 Hz), gamma (30-80 Hz), and high gamma (80-200 Hz) bands. RESULTS: Compared to isocitrate dehydrogenase (IDH) wild-type tumors, those with IDH-mutation (n = 3; two WHO grade 3, one grade 4) demonstrated the highest proportion of power within the LF band (92.2% vs 71.4%) with relatively lower proportional beta (3.6% vs 18.3%) and gamma (2.2% vs 8.7%) bandpower. The same pattern was seen in HGG (n = 5) vs LGG (n = 3) tumors with higher LF (84.5% vs 70.3%) and lower beta (10.3% vs 16.8%) and gamma (3.5% vs 10.8%) bandpower, perhaps driven by three HGGs with IDH mutation. Absolute bandpower was highest at all bands in a patient with left frontal glioblastoma. CONCLUSIONS: Interesting patterns are emerging that corroborate differential high and low frequency neural activity among patients with primary brain tumors. Disparities in LF and beta/gamma bands may represent therapeutic targets or a non-invasive biomarker of disease activity but require further, ongoing data collection and analyses.