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pmid:38476973
SIRT3 Expression Predicts Overall Survival and Neoadjuvant Chemosensitivity in Triple-Negative Breast Cancer.
Lvwen Ning · Ni Xie
Cancer management and research · 2024 doi:10.2147/CMAR.S445248
Paper
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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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SIRTs expression has been reported to have prognostic value in BC, but these studies used limited sample size and yielded inconsistent conclusions. This study evaluated the association of SIRT3 and other SIRT family members with survival and neoadjuvant chemotherapy outcomes.\nMethods: BC patients' data was obtained from the TCGA-BRCA, METABRIC and GEO databases, comprising 4336 samples. SIRTs expression and overall survival (OS) were analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. SIRT3 expression levels were compared between pathologic complete response (pCR) and non-pCR groups after neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Protein-protein interaction networks were constructed using the STRING database. Gene set enrichment analysis (GSEA) was performed to explore potential functions of SIRT3.\nResults: Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts. SIRT3 expression was correlated with BC subtypes and American Joint Committee on Cancer (AJCC) T stage, but not with age-at-diagnosis, race, or tumor stage. Moreover, TNBC patients with higher SIRT3 expression had lower pCR rates after neoadjuvant chemotherapy (p = 6.40e-03) and SIRT3 expression was significantly lower in the pCR group than in the non-pCR group in TNBC (p = 4.2e-03). GSEA indicated that SIRT3 was involved in drug-related pathways such as oxidative phosphorylation, metabolism of xenobiotics by cytochrome P450, and drug metabolism.\nConclusion: Our study suggests that SIRT3 is a potential biomarker for both OS and neoadjuvant chemosensitivity in TNBC. It may also assist in selecting suitable candidates and treatment options for TNBC patients.", "claims": [{"id": "claim-method", "statement": "We used the Python package lifelines (https://lifelines.readthedocs.io/en/latest/, version 0.26.4)25 to perform Kaplan–Meier curve, Log rank test, univariate and multivariate Cox proportional hazards regression analyses.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38476973", "locator": "sections[6] \"Survival Analysis\" paragraph 2", "quote": "We used the Python package lifelines (https://lifelines.readthedocs.io/en/latest/, version 0.26.4)25 to perform Kaplan–Meier curve, Log rank test, univariate and multivariate Cox proportional hazards regression analyses."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data were downloaded from public databases and followed the data access policies.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38476973", "locator": "sections[20] \"Data Sharing Statement\" paragraph 2", "quote": "All data were downloaded from public databases and followed the data access policies."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38476973", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Through systematic analysis of SIRTs expression and OS of BC using three independent cohorts: TCGA-BRCA, METABRIC and GSE16446, we found that high SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "High SIRT3 expression was significantly associated with worse OS in TNBC in the TCGA-BRCA cohort, which was validated in the METABRIC and GSE16446 cohorts.", "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:38476973"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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