bims-malgli Biomed News
on Biology of malignant gliomas
Issue of 2024–03–24
thirteen papers selected by
Oltea Sampetrean, Keio University
  1. Targeting the cell cycle to enhance chemotherapy efficacy in glioblastoma.
  2. ARF4-mediated retrograde trafficking as a driver of chemoresistance in GBM.
  3. Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.
  4. EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.
  5. Marizomib for patients with newly diagnosed glioblastoma: a randomized phase 3 trial.
  6. A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.
  7. IL-13Rα2-targeted CAR T cells show promise in patients with recurrent high-grade gliomas.
  8. Brain-wide neuronal circuit connectome of human glioblastoma.
  9. Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.
  10. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.
  11. RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.
  12. Spiking GABAergic OPC tumor cells prolong survival in IDH1 mutant glioma.
  13. Dietary patterns in relation to glioma: a case-control study.
  1. Neuro Oncol. 2024 Mar 22. pii: noae062. [Epub ahead of print]
    Targeting the cell cycle to enhance chemotherapy efficacy in glioblastoma.
    Matthew McCord, Pouya Jamshidi.
      
    DOI:  https://doi.org/10.1093/neuonc/noae062
  2. Neuro Oncol. 2024 Mar 20. pii: noae059. [Epub ahead of print]
    ARF4-mediated retrograde trafficking as a driver of chemoresistance in GBM.
    Shreya Budhiraja, Graysen McManus, Shivani Baisiwala, Ella N Perrault, Sia Cho, Miranda Saathoff, Li Chen, Cheol H Park, Hasaan A Kazi, Crismita Dmello, Peiyu Lin, C David James, Adam M Sonabend, Dieter H Heiland, Atique U Ahmed.
       BACKGROUND: Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear.
    METHODS: To identify genetic drivers of TMZ resistance, we conducted comprehensive CRISPR-knockout screening, revealing ADP-ribosylation factor 4 (ARF4), a regulator of retrograde trafficking, as a major contributor.
    RESULTS: Suppressing ARF4 significantly enhanced TMZ sensitivity in GBM patient-derived xenograft (PDX) models, leading to improved survival rates (p<0.01) in both primary and recurrent lines. We also observed that TMZ exposure stimulates ARF4-mediated retrograde trafficking. Proteomics analysis of GBM cells with varying levels of ARF4 unveiled the influence of this pathway on EGFR signaling, with increased nuclear trafficking of EGFR observed in cells with ARF4 overexpression and TMZ treatment. Additionally, spatially-resolved RNA-sequencing of GBM patient tissues revealed substantial correlations between ARF4 and crucial nuclear EGFR (nEGFR) downstream targets, such as MYC, STAT1, and DNA-PK. Decreased activity of DNA-PK, a DNA repair protein downstream of nEGFR signaling that contributes to TMZ resistance, was observed in cells with suppressed ARF4 levels. Notably, treatment with DNA-PK inhibitor, KU57788, in mice with a recurrent PDX line resulted in prolonged survival (p<0.01), highlighting the promising therapeutic implications of targeting proteins reliant on ARF4-mediated retrograde trafficking.
    CONCLUSION: Our findings demonstrate that ARF4-mediated retrograde trafficking contributes to the development of TMZ resistance, cementing this pathway as a viable strategy to overcome chemoresistance in GBM.
    Keywords:  ARF4; Glioblastoma; chemoresistance; retrograde trafficking; whole-genome CRISPR screen
    DOI:  https://doi.org/10.1093/neuonc/noae059
  3. Sci Transl Med. 2024 Mar 20. 16(739): eadg5553
    Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.
    Jianxing Yin, Xin Ge, Fangshu Ding, Liuguijie He, Keying Song, Zhumei Shi, Zehe Ge, Junxia Zhang, Jing Ji, Xiefeng Wang, Ningwei Zhao, Chuanjun Shu, Fan Lin, Qianghu Wang, Qigang Zhou, Yuandong Cao, Wentao Liu, Dan Ye, Jeremy N Rich, Xiuxing Wang, Yongping You, Xu Qian.
      Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.
    DOI:  https://doi.org/10.1126/scitranslmed.adg5553
  4. Neuro Oncol. 2024 Mar 20. pii: noae060. [Epub ahead of print]
    EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.
    Andrea Álvarez-Vázquez, Laura San-Segundo, Pilar Cerveró-García, Raquel Flores-Hernández, Claudia Ollauri-Ibáñez, Berta Segura-Collar, C G Hubert, Gillian Morrison, Steven M Pollard, Justin D Lathia, Pilar Sánchez-Gómez, Arantxa Tabernero.
       BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283.
    METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ) and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by Western blot (WB) and Fluorescence In Situ Hybridization (FISH) in these cells, and compared with Src activity and survival in GBM samples from TCGA.
    RESULTS: The effect of TAT-Cx43266-283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations, showed a decrease in growth, invasiveness and vascularization after treatment with TAT-Cx43266-283, which enhanced the survival of immunocompetent mice.
    CONCLUSION: Clinically relevant EGFR alterations are predictors of TAT-Cx43266-283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266-283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step towards the clinical application of TAT-Cx43266-283.
    Keywords:  EGFR; Glioblastoma; NSCs; Src; cell-penetrating peptides
    DOI:  https://doi.org/10.1093/neuonc/noae060
  5. Neuro Oncol. 2024 Mar 19. pii: noae053. [Epub ahead of print]
    Marizomib for patients with newly diagnosed glioblastoma: a randomized phase 3 trial.
    EORTC Brain Tumor Group and the Canadian Cancer Trials Group
       BACKGROUND: Standard treatment for patients with newly diagnosed glioblastoma includes surgery, radiotherapy (RT) and temozolomide (TMZ) chemotherapy (TMZ/RT→TMZ). The proteasome has long been considered a promising therapeutic target because of its role as a central biological hub in tumor cells. Marizomib is a novel pan-proteasome inhibitor that crosses the blood brain barrier.
    METHODS: EORTC 1709/CCTG CE.8 was a multicenter, randomized, controlled, open label phase 3 superiority trial. Key eligibility criteria included newly diagnosed glioblastoma, age > 18 years and Karnofsky performance status > 70. Patients were randomized in a 1:1 ratio. The primary objective was to compare overall survival (OS) in patients receiving marizomib in addition to TMZ/RT→TMZ with patients receiving only standard treatment in the whole population, and in the subgroup of patients with MGMT promoter-unmethylated tumors.
    RESULTS: The trial was opened at 82 institutions in Europe, Canada and the US. A total of 749 patients (99.9% of planned 750) were randomized. OS was not different between the standard and the marizomib arm (median 17 vs 16.5 months; HR=1.04; p=0.64). PFS was not statistically different either (median 6.0 vs. 6.3 months; HR=0.97; p=0.67). In patients with MGMT promoter-unmethylated tumors, OS was also not different between standard therapy and marizomib (median 14.5 vs 15.1 months, HR=1.13; p=0.27). More CTCAE grade 3/4 treatment-emergent adverse events were observed in the marizomib arm than in the standard arm.
    CONCLUSIONS: Adding marizomib to standard temozolomide-based radiochemotherapy resulted in more toxicity, but did not improve OS or PFS in patients with newly diagnosed glioblastoma.
    Keywords:  EORTC 1709; MGMT; glioma; proteasome inhibitor; randomized study
    DOI:  https://doi.org/10.1093/neuonc/noae053
  6. bioRxiv. 2024 Mar 08. pii: 2024.03.06.583588. [Epub ahead of print]
    A longitudinal single-cell and spatial multiomic atlas of pediatric high-grade glioma.
    Jonathan H Sussman, Derek A Oldridge, Wenbao Yu, Chia-Hui Chen, Abigail M Zellmer, Jiazhen Rong, Arianne Parvaresh-Rizi, Anusha Thadi, Jason Xu, Shovik Bandyopadhyay, Yusha Sun, David Wu, C Emerson Hunter, Stephanie Brosius, Kyung Jin Ahn, Amy E Baxter, Mateusz P Koptyra, Rami S Vanguri, Stephanie McGrory, Adam C Resnick, Phillip B Storm, Nduka M Amankulor, Mariarita Santi, Angela N Viaene, Nancy Zhang, Thomas De Raedt, Kristina Cole, Kai Tan.
      Pediatric high-grade glioma (pHGG) is an incurable central nervous system malignancy that is a leading cause of pediatric cancer death. While pHGG shares many similarities to adult glioma, it is increasingly recognized as a molecularly distinct, yet highly heterogeneous disease. In this study, we longitudinally profiled a molecularly diverse cohort of 16 pHGG patients before and after standard therapy through single-nucleus RNA and ATAC sequencing, whole-genome sequencing, and CODEX spatial proteomics to capture the evolution of the tumor microenvironment during progression following treatment. We found that the canonical neoplastic cell phenotypes of adult glioblastoma are insufficient to capture the range of tumor cell states in a pediatric cohort and observed differential tumor-myeloid interactions between malignant cell states. We identified key transcriptional regulators of pHGG cell states and did not observe the marked proneural to mesenchymal shift characteristic of adult glioblastoma. We showed that essential neuromodulators and the interferon response are upregulated post-therapy along with an increase in non-neoplastic oligodendrocytes. Through in vitro pharmacological perturbation, we demonstrated novel malignant cell-intrinsic targets. This multiomic atlas of longitudinal pHGG captures the key features of therapy response that support distinction from its adult counterpart and suggests therapeutic strategies which are targeted to pediatric gliomas.
    DOI:  https://doi.org/10.1101/2024.03.06.583588
  7. Nat Rev Clin Oncol. 2024 Mar 21.
    IL-13Rα2-targeted CAR T cells show promise in patients with recurrent high-grade gliomas.
    David Killock.
      
    DOI:  https://doi.org/10.1038/s41571-024-00885-z
  8. bioRxiv. 2024 Mar 04. pii: 2024.03.01.583047. [Epub ahead of print]
    Brain-wide neuronal circuit connectome of human glioblastoma.
    Yusha Sun, Xin Wang, Daniel Y Zhang, Zhijian Zhang, Janardhan P Bhattarai, Yingqi Wang, Weifan Dong, Feng Zhang, Kristen H Park, Jamie Galanaugh, Abhijeet Sambangi, Qian Yang, Sang Hoon Kim, Garrett Wheeler, Tiago Goncalves, Qing Wang, Daniel Geschwind, Riki Kawaguchi, Huadong Wang, Fuqiang Xu, Zev A Binder, Isaac H Chen, Emily Ling-Lin Pai, Sara Stone, MacLean Nasrallah, Kimberly M Christian, Marc Fuccillo, Donald M O'Rourke, Minghong Ma, Guo-Li Ming, Hongjun Song.
      Glioblastoma (GBM), a universally fatal brain cancer, infiltrates the brain and can be synaptically innervated by neurons, which drives tumor progression 1-6 . Synaptic inputs onto GBM cells identified so far are largely short-range and glutamatergic 7-9 . The extent of integration of GBM cells into brain-wide neuronal circuitry is not well understood. Here we applied a rabies virus-mediated retrograde monosynaptic tracing approach 10-12 to systematically investigate circuit integration of human GBM organoids transplanted into adult mice. We found that GBM cells from multiple patients rapidly integrated into brain-wide neuronal circuits and exhibited diverse local and long-range connectivity. Beyond glutamatergic inputs, we identified a variety of neuromodulatory inputs across the brain, including cholinergic inputs from the basal forebrain. Acute acetylcholine stimulation induced sustained calcium oscillations and long-lasting transcriptional reprogramming of GBM cells into a more invasive state via the metabotropic CHRM3 receptor. CHRM3 downregulation suppressed GBM cell invasion, proliferation, and survival in vitro and in vivo. Together, these results reveal the capacity of human GBM cells to rapidly and robustly integrate into anatomically and molecularly diverse neuronal circuitry in the adult brain and support a model wherein rapid synapse formation onto GBM cells and transient activation of upstream neurons may lead to a long-lasting increase in fitness to promote tumor infiltration and progression.
    DOI:  https://doi.org/10.1101/2024.03.01.583047
  9. Neuro Oncol. 2024 Mar 20. pii: noae061. [Epub ahead of print]
    Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.
    A Ryba, Z Özdemir, N Nissimov, L Hönikl, N Neidert, M Jakobs, D Kalasauskas, A Krigers, C Thomé, C F Freyschlag, F Ringel, A Unterberg, P Dao Trong, J Beck, D H Heiland, B Meyer, P Vajkoczy, J Onken, W Stummer, E Suero Molina, J Gempt, M Westphal, U Schüller, M Mohme.
       BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults.
    METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors.
    RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006).
    CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.
    Keywords:  H3 K27M; H3F3A; HIST1H3B; High-grade glioma; Histone H3
    DOI:  https://doi.org/10.1093/neuonc/noae061
  10. Sci Rep. 2024 03 16. 14(1): 6362
    Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.
    Takahide Nejo, Lin Wang, Kevin K Leung, Albert Wang, Senthilnath Lakshmanachetty, Marco Gallus, Darwin W Kwok, Chibo Hong, Lee H Chen, Diego A Carrera, Michael Y Zhang, Nicholas O Stevers, Gabriella C Maldonado, Akane Yamamichi, Payal B Watchmaker, Akul Naik, Anny Shai, Joanna J Phillips, Susan M Chang, Arun P Wiita, James A Wells, Joseph F Costello, Aaron A Diaz, Hideho Okada.
      Despite advancements in cancer immunotherapy, solid tumors remain formidable challenges. In glioma, profound inter- and intra-tumoral heterogeneity of antigen landscape hampers therapeutic development. Therefore, it is critical to consider alternative sources to expand the repertoire of targetable (neo-)antigens and improve therapeutic outcomes. Accumulating evidence suggests that tumor-specific alternative splicing (AS) could be an untapped reservoir of antigens. In this study, we investigated tumor-specific AS events in glioma, focusing on those predicted to generate major histocompatibility complex (MHC)-presentation-independent, cell-surface antigens that could be targeted by antibodies and chimeric antigen receptor-T cells. We systematically analyzed bulk RNA-sequencing datasets comparing 429 tumor samples (from The Cancer Genome Atlas) and 9166 normal tissue samples (from the Genotype-Tissue Expression project), and identified 13 AS events in 7 genes predicted to be expressed in more than 10% of the patients, including PTPRZ1 and BCAN, which were corroborated by an external RNA-sequencing dataset. Subsequently, we validated our predictions and elucidated the complexity of the isoforms using full-length transcript amplicon sequencing on patient-derived glioblastoma cells. However, analyses of the RNA-sequencing datasets of spatially mapped and longitudinally collected clinical tumor samples unveiled remarkable spatiotemporal heterogeneity of the candidate AS events. Furthermore, proteomics analysis did not reveal any peptide spectra matching the putative antigens. Our investigation illustrated the diverse characteristics of the tumor-specific AS events and the challenges of antigen exploration due to their notable spatiotemporal heterogeneity and elusive nature at the protein levels. Redirecting future efforts toward intracellular, MHC-presented antigens could offer a more viable avenue.
    Keywords:  Alternative splicing; Antigen; Bulk RNA-sequencing; Glioma; Intratumoral heterogeneity; Long-read sequencing; Neojunction; Proteomics
    DOI:  https://doi.org/10.1038/s41598-024-56684-0
  11. Cell Discov. 2024 Mar 19. 10(1): 32
    RBBP6 maintains glioblastoma stem cells through CPSF3-dependent alternative polyadenylation.
    Peng Lin, Wenyan Chen, Zhilin Long, Jichuan Yu, Jiayao Yang, Zhen Xia, Qiulian Wu, Xinyu Min, Jing Tang, Ya Cui, Fuyi Liu, Chun Wang, Jian Zheng, Wei Li, Jeremy N Rich, Lei Li, Qi Xie.
      Glioblastoma is one of the most lethal malignant cancers, displaying striking intratumor heterogeneity, with glioblastoma stem cells (GSCs) contributing to tumorigenesis and therapeutic resistance. Pharmacologic modulators of ubiquitin ligases and deubiquitinases are under development for cancer and other diseases. Here, we performed parallel in vitro and in vivo CRISPR/Cas9 knockout screens targeting human ubiquitin E3 ligases and deubiquitinases, revealing the E3 ligase RBBP6 as an essential factor for GSC maintenance. Targeting RBBP6 inhibited GSC proliferation and tumor initiation. Mechanistically, RBBP6 mediated K63-linked ubiquitination of Cleavage and Polyadenylation Specific Factor 3 (CPSF3), which stabilized CPSF3 to regulate alternative polyadenylation events. RBBP6 depletion induced shortening of the 3'UTRs of MYC competing-endogenous RNAs to release miR-590-3p from shortened UTRs, thereby decreasing MYC expression. Targeting CPSF3 with a small molecular inhibitor (JTE-607) reduces GSC viability and inhibits in vivo tumor growth. Collectively, RBBP6 maintains high MYC expression in GSCs through regulation of CPSF3-dependent alternative polyadenylation, providing a potential therapeutic paradigm for glioblastoma.
    DOI:  https://doi.org/10.1038/s41421-024-00654-3
  12. bioRxiv. 2024 Mar 06. pii: 2024.03.02.583026. [Epub ahead of print]
    Spiking GABAergic OPC tumor cells prolong survival in IDH1 mutant glioma.
    Rachel Naomi Curry, Qianqian Ma, Malcolm F McDonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Isamu Aiba, Jochen Meyer, Junzhan Jing, Su Wang, Arif O Harmanci, Prazwal Athukuri, Jeffrey Noebels, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci.
      Prior studies have shown that glioma cells form synapses with neurons to receive synaptic inputs. To discern if glioma cells can send outgoing electrochemical signals in the form of action potentials (APs), we employed Patch-sequencing on surgically-resected human glioma slices. Results showed that half of patched cells in IDH1 mutant (IDH1 mut ) tumors demonstrate select properties of both neurons and glia and fire single, short APs. To define the transcriptional profiles of these hybrid cells (HCs) and discern if they are tumor derived, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate features in each cell individually. SCRAM revealed that HCs represent a heterogenous group of tumor and non-tumor cells that are uniformly defined by both GABAergic neuron and oligodendrocyte precursor cell (GABA-OPC) transcriptional signatures. We found that GABA-OPC tumor cells express requisite voltage-gated ion channels needed to fire APs. We validated our findings in human single cell and bulk RNA-seq datasets, confirming that GABA-OPCs represent 40% of IDH1 mut tumor cells, correlate with survival outcomes in IDH1 mut human patients and are also found in select molecular subtypes of IDH1 wild-type tumors. These studies describe a new cell type in IDH1 mut glioma with unique electrophysiological and transcriptomic properties.
    DOI:  https://doi.org/10.1101/2024.03.02.583026
  13. Cancer Metab. 2024 Mar 18. 12(1): 8
    Dietary patterns in relation to glioma: a case-control study.
    Mohammad Nemati, Mehdi Shayanfar, Fatemeh Almasi, Minoo Mohammad-Shirazi, Giuve Sharifi, Azadeh Aminianfar, Ahmad Esmaillzadeh.
      Although the association of individual foods and nutrients with glioma have been investigated, studies on the association of major dietary patterns and glioma are scarce. The aim of this study was to examine the association between major dietary patterns and risk of glioma in a group of Iranian adults. In this hospital-based case-control design, we recruited 128 newly diagnosed glioma cases and 256 controls in Tehran from 2009 to 2011. A Willett-format-validated 126-item semi-quantitative Food Frequency Questionnaire (FFQ) was used to assess participants' dietary intake. Factor analysis was used to identify major dietary patterns. We identified 3 major dietary patterns using factor analysis: high protein, vegetarian and western dietary pattern. After several adjustments for potential confounders, adherence to the high protein dietary pattern was inversely associated with risk of glioma (OR: 0.47; 95% CI: 0.23, 0.95). Consumption of vegetarian dietary pattern was also associated with a reduced risk of glioma (OR: 0.16; 95% CI: 0.07, 0.34). Greater adherence to the western dietary pattern was associated with a greater chance of glioma (OR: 3.30; 95% CI: 1.52, 7.17). We found that high protein, vegetarian and western dietary pattern were significantly associated with glioma risk. Further prospective studies are needed to confirm these findings.
    Keywords:  Brain tumor; Cancer; Case–control; Diet; Dietary pattern; Glioma; High protein; Vegetarian; Western
    DOI:  https://doi.org/10.1186/s40170-024-00336-4
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