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pmid:39708330
Deciphering the Significance of Platelet-Derived Chloride Ion Channel Gene (BEST3) Through Platelet-Related Subtypes Mining for Non-Small Cell Lung Cancer.
Hanxiao Ren · Meng-Ze Du · Yulin Liao · Ruiling Zu · Lubei Rao · Run Xiang · Xingmei Zhang · Shan Liu · Peiyin Zhang · Ping Leng · Ling Qi · Huaichao Luo
Journal of cellular and molecular medicine · 2024 doi:10.1111/jcmm.70233
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Complete file
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We utilised sequencing and clinical data from GEO, TCGA and the Xena platform, building a risk model based on genetic features. TCGA and GSE37745 served as training cohorts, while GSE50081, GSE13213, GSE30129 and GSE42127 were validation cohorts. Immunotherapy datasets (GSE135222, TCGA-SKCM) were also analysed. Differentially expressed genes (DEGs) were identified using Limma, subtypes through ConsensusClusterPlus and key prognostic genes using COX regression, Random Forest and LASSO-COX. BEST3 expression was validated by flow cytometry (FCM) and functional assays in A549 cells with lentiviral overexpression evaluated its impact on apoptosis, proliferation and migration. Three platelet-related subtypes were identified, with ten key prognostic genes (including BEST3). Gene Ontology (GO) analysis showed six genes involved in platelet pathways. BEST3 was highly expressed in the platelet subtype 1. Flow cytometry confirmed elevated BEST3 levels in NSCLC (35.9% vs. 27.3% in healthy individuals). Overexpression of BEST3 in NSCLC cells suppressed apoptosis and promoted proliferation and migration. The discovery of three platelet subtypes and the role of BEST3 in promoting tumour growth and migration highlights its potential as a therapeutic target and prognostic marker in NSCLC.", "claims": [{"id": "claim-method", "statement": "Survival analysis curves were plotted with Kaplan–Meier, and log‐rank tests were applied to compare OS differences between groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39708330", "locator": "sections[15] \"Data Analysis and Statistical Methods\" paragraph 2", "quote": "Survival analysis curves were plotted with Kaplan–Meier, and log‐rank tests were applied to compare OS differences between groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data from study are included in this manuscript. 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BEST3 expression was validated by flow cytometry (FCM) and functional assays in A549 cells wi", "highly expressed in the platelet subtype 1. Flow cytometry confirmed elevated BEST3 levels in NSCLC (35"], "order_basis": "paper_text_order:860", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["low cytometry (FCM) and functional assays in A549 cells with lentiviral overexpression evaluat", "rmo Fisher Scientific). Cells were routinely cultured in DMEM (Gibco, #C11995500BT) or 1640 medium (V", "Materials and Methods Cell Culture A549 cells were maintained at 37°C in a 5% CO₂ in"], "order_basis": "paper_text_order:906", "id": "assay:2"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["viral overexpression evaluated its impact on apoptosis, proliferation and migration. Three platelet", "xpression of BEST3 in NSCLC cells suppressed apoptosis and promoted proliferation and migration. 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