Evidence map›Paper›PMID 30914782›Full record

ArticleLaboratory investigation; a journal of technical methods and pathology2019

B7H3 regulates differentiation and serves as a potential biomarker and theranostic target for human glioblastoma.

Jingwen Zhang, Jinhua Wang, Diego M Marzese, Xiaowen Wang, Zixiao Yang, Chunjie Li, Haibo Zhang, Jinsen Zhang, Clark C Chen, Daniel F Kelly and 3 more

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Jingwen ZhangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Jinhua WangDepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI) at Providence Saint John's Health Center(SJHC), Santa Monica, CA, USA.
Diego M MarzeseDepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI) at Providence Saint John's Health Center(SJHC), Santa Monica, CA, USA.ORCID http://orcid.org/0000-0002-3258-8852
Xiaowen WangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Zixiao YangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Chunjie LiDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Haibo ZhangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Jinsen ZhangDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Clark C ChenDepartment of Neurosurgery, University of Minnesota, Minneapolis, MN, USA.
Daniel F KellyBrain Tumor Center and Pituitary Disorders Program, JWCI at Providence SJHC, Santa Monica, CA, USA.
Wei HuaDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China. hs_glioma@126.com.
Dave S B HoonDepartment of Translational Molecular Medicine, John Wayne Cancer Institute (JWCI) at Providence Saint John's Health Center(SJHC), Santa Monica, CA, USA.
Ying MaoDepartment of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China.
Fudan University · CNSaint John's Health Center · USProvidence College · USUniversity of Minnesota · US

Funding

Targeting Mechanisms of Acquired Temozolomide Resistance in GlioblastomaR01NS097649 · NINDS · UNIVERSITY OF MINNESOTA · PI CHEN, CLARK CHIN-CHUNG · 2016 to 2021
$1.7M
NINDS NIH HHS R01 NS097649
6 · The paper itself

Abstract

B7H3 (CD276), a co-stimulator molecule of the cell surface B7 protein superfamily, is expressed on glioblastomas (GBM). Recently, B7H3 functions beyond immune costimulation have been demonstrated. However, the mechanisms underlying B7H3 function are diverse and not well understood. GBM tumors contain undifferentiated self-renewing cells, which confound therapeutic attempts. We investigated the role of B7H3 in the regulation of GBM cell differentiation and the regulatory pathways involved. Analysis of public databases (TCGA, Rembrandt, and GEO NCBI) and RNA sequencing were performed to explore the role of B7H3 in GBM. Knockdown and overexpression of B7H3, were used to verify the downstream pathway in vitro. Further studies in vivo were performed to support the new finding. Bioinformatics analysis identified a correlation between the expression of B7H3, the expression of glioma self-renewing cell (GSC)-related genes, and MYC expression. These observations were verified by RNA-sequencing analyses in primary GBM cell lines. In vitro knockdown of B7H3-induced differentiation, associated with downregulation of SMAD6 (a TGF-β pathway inhibitor) and enhancement of SMAD1 phosphorylation-induced SMAD4 expression. Importantly, activation of the TGF-β pathway resulted in downregulation of MYC expression. In vivo assays conducted in a human GBM cell line xenograft mouse model demonstrated that B7H3 knockdown decreased MYC expression and inhibited tumor growth. B7H3 knockdown could regulate GBM differentiation by modulating MYC expression. So, B7H3 could serve as a potential theranostic target for the treatment of patients with GBM.

Indexed as

B7 AntigensAnimalsBiomarkers, TumorBrain NeoplasmsCell DifferentiationCell Line, TumorFemaleGene Knockdown TechniquesGlioblastomaHumansMiceMice, NudeTranscriptomeXenograft Model Antitumor AssaysB7 AntigensBiomarkers, TumorCD276 protein, human

Identifiers

PMID30914782
OpenAlexW2923308008

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.