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pmid:34540835
Identification of ARHGEF38, NETO2, GOLM1, and SAPCD2 Associated With Prostate Cancer Progression by Bioinformatic Analysis and Experimental Validation.
Zhuolun Sun · Yunhua Mao · Xu Zhang · Shuo Lu · Hua Wang · Chi Zhang · Chutian Xiao · Yinghao Cao · Yunhao Qing · Yu Wang · Ke Li
Frontiers in cell and developmental biology · 2021 doi:10.3389/fcell.2021.718638
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Experiment
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Complete file
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The pathogenic mechanisms of PCa still need further investigation. The aim of this study was to construct an effective signature to predict the prognosis of PCa patients and identify the biofunctions of signature-related genes. First, we screened differentially expressed genes (DEGs) between PCa and normal control tissues in The Cancer Genome Atlas (TCGA) and GSE46602 datasets, and we performed weighted gene co-expression network analysis (WGCNA) to determine gene modules correlated with tumors. In total, 124 differentially co-expressed genes were retained. Additionally, five genes (ARHGEF38, NETO2, PRSS21, GOLM1, and SAPCD2) were identified to develop the prognostic signature based on TCGA dataset. The five-gene risk score was verified as an independent prognostic indicator through multivariate Cox regression analyses. The expression of the five genes involved in the signature was detected in the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine databases. In addition, we utilized DiseaseMeth 2.0 and MEXPRESS for further analysis and found that abnormal methylation patterns may be a potential mechanism for these five DEGs in PCa. Finally, we observed that these genes, except PRSS21, were highly expressed in tumor samples and PCa cells. Functional experiments revealed that silencing ARHGEF38, NETO2, GOLM1, and SAPCD2 suppressed the proliferation, migration, and invasiveness of PCa cells. In summary, this prognostic signature had significant clinical significance for treatment planning and prognostic evaluation of patients with PCa. Thus, ARHGEF38, NETO2, GOLM1, and SAPCD2 may serve as oncogenes in PCa.", "claims": [{"id": "claim-method", "statement": "The “limma” package was utilized to identify the DEGs between PCa tissues and normal tissues in both TCGA and GSE46602 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34540835", "locator": "sections[4] \"Analysis of DEGs Between PCa and Normal Samples\" paragraph 2", "quote": "The “limma” package was utilized to identify the DEGs between PCa tissues and normal tissues in both TCGA and GSE46602 datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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Written informed consent"], "order_basis": "paper_text_order:2831", "id": "assay:1"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["un Yat-sen University. Cell Culture and Cell Transfection One normal prostate epithelial cell line (RW", "density of 60–70%, 22Rv1 and PC-3 cells were transfected with these siRNAs using Lipofectamine 3000 a", "urther experiments were performed 48 h after transfection. Statistical Analysis All data were analyzed"], "order_basis": "paper_text_order:3064", "id": "assay:2"}, {"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": ["dium (K-SFM) (Thermo Fisher Scientific). All cell lines were grown in a 5% CO2-humidified incubator at 37°C. Th", "on (ATCC, VA, United States). PCa cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM, Th", "bovine serum (FBS), while RWPE-1 cells were cultured in supplemented keratinocyte serum-free medium"], "order_basis": "paper_text_order:3265", "id": "assay:3"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “limma” package was utilized to identify the DEGs between PCa tissues and normal tissues in both TCGA and GSE46602 datasets."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}