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:Intravenous leiomyomatosis (IVL) is an unusual uterine smooth muscle proliferation that can be associated with aggressive clinical behavior despite a histologically benign appearance. It has some overlapping molecular characteristics with both uterine leiomyoma and leiomyosarcoma based on limited genetic data. In this study, we assessed the clinical and morphological characteristics of 28 IVL and their correlation with molecular features and protein expression, using array comparative genomic hybridization (aCGH) and Cyclin D1, p16, phosphorylated-Rb, SMARCB1, SOX10, CAIX, SDHB and FH immunohistochemistry. The most common morphologies were cellular (n = 15), usual (n = 11), and vascular (n = 5; including 3 cellular IVL showing both vascular and cellular features). Among the immunohistochemical findings, the most striking was that all IVL showed differential expression of either p16 or Cyclin D1 in comparison to surrounding nonneoplastic tissue. Cytoplasmic phosphorylated-Rb was present in all but one IVL with hyalinization. SMARCB1, FH, and SDHB were retained; S0X10 and CAIX were not expressed. The most common genetic alterations involved 1p (39%), 22q (36%), 2q (29%), 1q (25%), 13q (21%), and 14q (21%). Hierarchical clustering analysis of recurrent aberrations revealed three molecular groups: Groups 1 (29%) and 2 (18%) with associated del(22q), and Group 3 (18%) with del(10q). The remaining IVL had nonspecific or no alterations by aCGH. Genomic index scores were calculated for all cases and showed no significant difference between the 14 IVL associated with aggressive clinical behavior (extrauterine extension or recurrence) and those without (median scores 5.15 vs 3.5). Among the 5 IVL associated with recurrence, 4 had a vascular morphology and 3 had alterations of 8q. Recurrent chromosome alterations detected herein overlap with those observed in the spectrum of uterine smooth muscle tumors and involve genes implicated in mesenchymal tumors at different sites with distinct morphological features.

Dataset Information

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

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

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