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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:The World Health Organization characterizes human choroid plexus tumor (CPT) as papilloma (CPP), atypical CPP (ACPP), and carcinoma (CPC). CPCs can disseminate via cerebrospinal fluid and be mistaken for metastatic carcinoma, creating a diagnostic challenge. Kir7.1 immunohistochemistry (IHC) is a highly reliable tool for diagnostic confirmation of CPTs and their differentiation from metastatic carcinomas in human beings and dogs. This study describes the neuropathology, Kir7.1 staining profile, and the immune cell population within the tumor microenvironment in 11 CPTs in dogs. Archived tissue sections with a diagnosis of CPT were examined and immunolabelled with Kir7.1 for diagnostic confirmation. The number of Ki67-positive neoplastic cells was calculated in 2.4 mm2 (equivalent to 10 FN22/40X fields), and a mean value was generated for each neoplasm. IHC for CD3, CD20, MAC387, and Iba1 was performed for immune cell characterization, and the number of stained cells for each antibody was counted in 2.4 mm2, generating individual cumulative values for each antibody. T-tests with Bonferroni correction evaluated IHC differences between tumor types, and Spearman's rank correlations evaluated relationships among IHC markers. Kir7.1 immunoreactivity was intense at the apical cell membrane in CPPs and ACPPs, and at the apical cell membrane and cytoplasm in CPCs. Ki67 immunoreactivity was detected in all cases. CD3+ and CD20+ lymphocytes trended together (p = 0.005) and were present within and around all CPTs. Five cases had intravascular MAC387+ monocytes. Iba1 immunoreactivity was robust within and around all tumors. Statistical differences in immune cell markers were not found among tumor types. As previously reported, Kir7.1 is a reliable antibody for the diagnosis of canine CPTs. Although immune cells were present in all cases, no significant associations were found between the type of cells and tumor diagnosis. The characterization of the immune cells within CPTs could be useful in future studies involving immunotherapy.

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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