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pmid:37170211
BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma.
Chiyi Jiang · Yeran Yang · Sidou He · Zhixia Yue · Tianyu Xing · Ping Chu · Wenfa Yang · Hui Chen · Xiaoxi Zhao · Yongbo Yu · Xuan Zhang · Yan Su · Yongli Guo · Xiaoli Ma
Biological procedures online · 2023 doi:10.1186/s12575-023-00200-7
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Experiment
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Complete file
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BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB.\nMETHODS: The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels.\nRESULTS: Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression.\nCONCLUSIONS: A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.", "claims": [{"id": "claim-method", "statement": "The Kaplan–Meier method was used to estimate Event-free survival (EFS) and Overall survival (OS), which were regarded as relapse-progression outcome indicator. Group difference was calculated with the log-rank test. 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More data are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "BPTF is an independent risk factor for predicting NB progression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37170211", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "BPTF is an independent risk factor for predicting NB progression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "BPTF is an independent risk factor for predicting NB progression.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37170211"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62564"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE62564"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37170211", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12575-023-00200-7", "sha256": "sha256:080543b4429291db4f2e1b2eeaf9534cc5e4136c03f3073a80687dfd9bc40d49", "bytes": 47925, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12575-023-00200-7", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10176855", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE62564", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE62564", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE62564", "version": null, "note": "Datasets and other files generated or analyzed during this study are included in this article and its supplementary files. 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It is routinely cultured in DMEM medium containing 10% fetal bovine seru", "l culture Human NB cell line SK-N-BE (2) and SH-SY5Y were purchased from American type culture co"], "order_basis": "paper_text_order:3802", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The Kaplan–Meier method was used to estimate Event-free survival (EFS) and Overall survival (OS), which were regarded as relapse-progression outcome indicator. Group difference was calculated with the log-rank test. Univariate and multivariate COX regression were conducted to analyse the risk factors for EFS."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}