Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

Quantitative Proteomic Analysis of Meningiomas for the Identification of Surrogate Protein Markers

Meningiomas are the most common non-glial tumors of the brain and spine. Pathophysiology and definite histological grading of meningiomas are frequently found to be deceptive due to their unusual morphological features and locations. Here for the first time we report a comprehensive serum proteomic analysis of different grades of meningiomas by using multiple quantitative proteomic and immunoassay-based approaches to obtain mechanistic insights about disease pathogenesis and identify grade specific protein signatures. In silico functional analysis revealed modulation of different vital physiological pathways including complement and coagulation cascades, metabolism of lipids and lipoproteins, immune signaling, cell growth and apoptosis and integrin signaling in meningiomas. ROC curve analysis demonstrated apolipoprotein E and A-I and hemopexin as efficient predictors for meningiomas. Identified proteins like vimentin, alpha-2-macroglobulin, apolipoprotein B and A-I and antithrombin-III, which exhibited a sequential increase in different malignancy grades of meningiomas, could serve as potential predictive markers

Multi-pronged proteomic analysis to study the glioma pathobiology using cerebrospinal fluid samples

PurposeGliomas are one of the most aggressive and lethal brain tumors arising from neoplastic transformation of astrocytes and oligodendrocytes. A comprehensive quantitative analysis of proteome level differences in cerebrospinal fluid (CSF) across different grades of gliomas for a better understanding of glioma pathobiology is carried out. Experimental designGlioma patients are diagnosed by radiology and histochemistry-based analyses. Differential proteomic analysis of high (n = 12) and low (n = 8) grade gliomas, and control (n = 3) samples is performed by using two complementary quantitative proteomic approaches; 2D-DIGE and iTRAQ. Further, comparative analysis of three IDH wild-type and five IDH mutants is performed to identify the proteome level differences between these two sub-classes. ResultsLevel of several proteins including haptoglobin, transthyretin, osteopontin, vitronectin, complement factor H and different classes of immunoglobulins are found to be considerably increased in CSF of higher grades of gliomas. Subsequent bioinformatics analysis indicated that many of the dysregulated CSF proteins are associated with metabolism of lipids and lipoproteins, complement and coagulation cascades and extracellular matrix remodeling in gliomas. Intriguingly, CSF of glioma patients with IDH mutations exhibite increased levels of multiple proteins involved in response to oxidative stress. Conclusion and clinical relevanceTo the best of our knowledge, this is the foremost proteome level investigation describing comprehensive proteome profiles of different grades of gliomas using proximal fluid (CSF); and thereby providing insights into disease pathobiology, which aided in identification of grade and sub-type specific alterations. Moreover, if validated in larger clinical cohorts, a panel of differentially abundant CSF proteins may serve as potential disease monitoring and prognostic markers for gliomas

Subventricular zone involvement in Glioblastoma - A proteomic evaluation and clinicoradiological correlation

Glioblastoma multiforme (GBM), the most malignant of all gliomas is characterized by a high degree of heterogeneity and poor response to treatment. The sub-ventricular zone (SVZ) is the major site of neurogenesis in the brain and is rich in neural stem cells. Based on the proximity of the GBM tumors to the SVZ, the tumors can be further classified into SVZ+ and SVZ-. The tumors located in close contact with the SVZ are classified as SVZ+, while the tumors located distantly from the SVZ are classified as SVZ-. To gain an insight into the increased aggressiveness of SVZ+ over SVZ - tumors, we have used proteomics techniques like 2D-DIGE and LC-MS/MS to investigate any possible proteomic differences between the two subtypes. Serum proteomic analysis revealed significant alterations of various acute phase proteins and lipid carrying proteins, while tissue proteomic analysis revealed significant alterations in cytoskeletal, lipid binding, chaperone and cell cycle regulating proteins, which are already known to be associated with disease pathobiology. These findings provide cues to molecular basis behind increased aggressiveness of SVZ + GBM tumors over SVZ - GBM tumors and plausible therapeutic targets to improve treatment modalities for these highly invasive tumors

Autoantibody Profiling of Glioma Serum Samples to Identify Biomarkers Using Human Proteome Arrays

The heterogeneity and poor prognosis associated with gliomas, makes biomarker identification imperative. Here, we report autoantibody signatures across various grades of glioma serum samples and sub-categories of glioblastoma multiforme using Human Proteome chips containing similar to 17000 fulllength human proteins. The deduced sets of classifier proteins helped to distinguish Grade II, III and IV samples from the healthy subjects with 88, 89 and 94% sensitivity and 87, 100 and 73% specificity, respectively. Proteins namely, SNX1, EYA1, PQBP1 and IGHG1 showed dysregulation across various grades. Sub-classes of GBM, based on its proximity to the sub-ventricular zone, have been reported to have different prognostic outcomes. To this end, we identified dysregulation of NEDD9, a protein involved in cell migration, with probable prognostic potential. Another subcategory of patients where the IDH1 gene is mutated, are known to have better prognosis as compared to patients carrying the wild type gene. On a comparison of these two cohorts, we found STUB1 and YWHAH proteins dysregulated in Grade II glioma patients. In addition to common pathways associated with tumourigenesis, we found enrichment of immunoregulatory and cytoskeletal remodelling pathways, emphasizing the need to explore biochemical alterations arising due to autoimmune responses in glioma