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pmid:35999846
A cholesterogenic gene signature for predicting the prognosis of young breast cancer patients.
Xiaoping Li · Chaorong Zhou · Chaoran Qiu · Weiwen Li · Qihe Yu · Hui Huang · Yiwen Zhang · Xin Zhang · Liangliang Ren · Xin Huang · Qinghua Zhou
PeerJ · 2022 doi:10.7717/peerj.13922
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Experiment
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Data
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Analysis
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Complete file
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Differentially expressed genes (DEGs) were compared between tumour tissue (n = 183) and normal tissue (n = 30). By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis. Subgroup analysis and external validations of GSE131769 from the Gene Expression Omnibus (GEO) were performed to verify the signature. Subsequently, in experiment part, cell experiments were performed to further verify the biological roles of the five cholesterogenic genes in BC.\nResults: In the bioinformatic section, a total of 97 upregulated genes and 124 downregulated cholesterogenic genes were screened as DEGs in the TCGA for training the model. A risk scoring signature contained five cholesterogenic genes (risk score = -1.169 × GRAMD1C -0.992 × NFKBIA + 0.432 × INHBA + 0.261 × CD24 -0.839 × ACSS2) was established, which could differentiate the prognosis of young BC patients between high-risk and low-risk group (<0.001). The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset. Then the prediction value of the signature was verified in GSE131769 with P = 0.033. In experiment part, although the downregulation of CD24, GRAMD1C and ACSS2 did not significantly affect cell viability, NFKBIA downregulation promoted the viability, colony forming ability and invasion capability of BC cells, while INHBA downregulation had the opposite effects.\nConclusion: The five-cholesterogenic-gene signature had independent prognostic value and robust reliability in predicting the prognosis of young BC patients. The cell experiment results suggested that NFKBIA played a protective role, while INHBA played the pro-cancer role in breast cancer.", "claims": [{"id": "claim-method", "statement": "By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "By using univariate Cox regression and multi COX regression, a five-cholesterogenic-gene signature was established to predict prognosis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data are available in the Supplementary File.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[24] \"Additional Information and Declarations\" paragraph 5", "quote": "The raw data are available in the Supplementary File."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.", "kind": "quantitative", "target": {"value": 0.81, "unit": "auc", "tolerance": null, "source": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset."}, "evidence": [{"asset": "source:pmid:35999846", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The prediction value of chelesterogenic gene signature in excellent with AUC was 0.810 in TCGA dataset.", "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:35999846"], "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. 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