Dataset Information

Immune heterogeneity and clinicopathologic characterization of IGFBP2 in 2447 glioma samples.

ABSTRACT: Glioblastoma is an immunosuppressive, deadly brain tumor. IGFBP2, a circulating biomarker for cancer diagnosis and a potential immunotherapeutic target, is attracting more and more attention from oncologists and clinicians. Thus, it is urgent to thoroughly investigate the immune biological process of IGFBP2 to understand tumor immune complexity and provide potential evidence for anti-IGFBP2 therapy. Through authoritative public databases, we enrolled a total of 2447 glioma samples with gene expression profiles. Then, the clinical characteristics and immunosuppressive status of IGFBP2 in the glioma samples were analyzed. Immunohistochemical staining detected the expression of immunosuppressive biomarkers. We found that IGFBP2 expression was upregulated in high-grade glioma and GBM and downregulated in IDH mutant glioma. Increased IGFBP2 accompanied PTEN loss and EGFR amplification. Bioinformatic analysis revealed that IGFBP2 is related to immunological processes. We further selected specific immunologic related gene sets and found IGFBP2 predominated immunosuppressive activities in GBM. Furthermore, we explored the relationship between IGFBP2 and genes that were well-characterized glioma-mediated immunosuppressive molecules to investigate the potential effect of IGFBP2. We discovered that IGFBP2 was correlated with CHI3L1, TNFRSF1A, LGALS1, TIMP1, VEGFA, ANXA1 and LGALS3, which were classic immunosuppressive biomarkers. Higher IGFBP2 expression predicted unfavorable survival for patients with GBM. Our findings implied that IGFBP2 is involved in immunosuppressive activities and is an independent unfavorable prognostic biomarker for patients with GBM. IGFBP2 is a potential immunotherapeutic target for GBM in future clinical trials.

SUBMITTER: Cai J

PROVIDER: S-EPMC5927515 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Immune heterogeneity and clinicopathologic characterization of IGFBP2 in 2447 glioma samples.

Cai Jinquan J Chen Qun Q Cui Yuqiong Y Dong Jiawei J Chen Meng M Wu Pengfei P Jiang Chuanlu C

Oncoimmunology 20180213 5

Glioblastoma is an immunosuppressive, deadly brain tumor. IGFBP2, a circulating biomarker for cancer diagnosis and a potential immunotherapeutic target, is attracting more and more attention from oncologists and clinicians. Thus, it is urgent to thoroughly investigate the immune biological process of IGFBP2 to understand tumor immune complexity and provide potential evidence for anti-IGFBP2 therapy. Through authoritative public databases, we enrolled a total of 2447 glioma samples with gene expr ...[more]

PMID: 29721393

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Project description:ImportanceFactors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement.ObjectivesTo examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy.Design, setting, and participantsThis cross-sectional study was a retrospective medical record review performed on the Florida Autopsied Multiethnic (FLAME) cohort accessioned from 1991 to 2020. Data were analyzed from December 2022 to December 2023. Structural magnetic resonance imaging (MRI) and tau positron emission tomography (PET) were evaluated in an independent neuroimaging group. The FLAME cohort includes 2809 autopsied individuals; included in this study were neuropathologically diagnosed AD cases (FLAME-AD). A digital pathology subgroup of FLAME-AD cases was derived for glial activation analyses.Main outcomes and measuresClinicopathologic factors of heterogeneity that inform patient history and neuropathologic evaluation of AD; CLix score (lower, relative cortical predominance/hippocampal sparing vs higher, relative cortical sparing/limbic predominant cases); neuroimaging measures (ie, structural MRI and tau-PET).ResultsOf the 2809 autopsied individuals in the FLAME cohort, 1361 neuropathologically diagnosed AD cases were evaluated. A digital pathology subgroup included 60 FLAME-AD cases. The independent neuroimaging group included 93 cases. Among the 1361 FLAME-AD cases, 633 were male (47%; median [range] age at death, 81 [54-96] years) and 728 were female (53%; median [range] age at death, 81 [53-102] years). A younger symptomatic onset (Spearman ρ = 0.39, P < .001) and faster decline on the Mini-Mental State Examination (Spearman ρ = 0.27; P < .001) correlated with a lower CLix score in FLAME-AD series. Cases with a nonamnestic syndrome had lower CLix scores (median [IQR], 13 [9-18]) vs not (median [IQR], 21 [15-27]; P < .001). Hippocampal MRI volume (Spearman ρ = -0.45; P < .001) and flortaucipir tau-PET uptake in posterior cingulate and precuneus cortex (Spearman ρ = -0.74; P < .001) inversely correlated with CLix score. Although AD cases with a CLix score less than 10 had higher cortical tangle count, we found lower percentage of CD68-activated microglia/macrophage burden (median [IQR], 0.46% [0.32%-0.75%]) compared with cases with a CLix score of 10 to 30 (median [IQR], 0.75% [0.51%-0.98%]) and on par with a CLix score of 30 or greater (median [IQR], 0.40% [0.32%-0.57%]; P = .02).Conclusions and relevanceFindings show that AD heterogeneity exists along a continuum of corticolimbic tangle distribution. Reduced CD68 burden may signify an underappreciated association between tau accumulation and microglia/macrophages activation that should be considered in personalized therapy for immune dysregulation.

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Dataset Information

Immune heterogeneity and clinicopathologic characterization of IGFBP2 in 2447 glioma samples.

Publications

Immune heterogeneity and clinicopathologic characterization of IGFBP2 in 2447 glioma samples.

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