SIRT3 Expression Predicts Overall Survival and Neoadjuvant Chemosensitivity in Triple-Negative Breast Cancer

IF 2.5 4区医学 Q3 ONCOLOGY

Cancer Management and Research Pub Date : 2024-03-08 DOI:10.2147/cmar.s445248

Lvwen Ning, Ni Xie

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引用次数: 0

Abstract

Background: The Sirtuin (SIRT) family consists of seven evolutionary conserved NAD-dependent deacetylases that play important roles in various cancers, including breast cancer (BC). 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.
Methods: 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.
Results: 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.
Conclusion: 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.

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SIRT3 表达可预测三阴性乳腺癌的总生存期和新辅助化疗敏感性

背景：Sirtuin（SIRT）家族由七种进化保守的NAD依赖性去乙酰化酶组成，在包括乳腺癌（BC）在内的多种癌症中发挥着重要作用。据报道，SIRTs的表达对乳腺癌有预后价值，但这些研究使用的样本量有限，得出的结论也不一致。本研究评估了SIRT3和其他SIRT家族成员与生存和新辅助化疗结果的关系：BC 患者数据来自 TCGA-BRCA、METABRIC 和 GEO 数据库，共 4336 个样本。采用Kaplan-Meier分析和Cox比例危险度回归分析SIRTs表达和总生存率（OS）。比较了三阴性乳腺癌（TNBC）新辅助化疗后病理完全反应组（pCR）和非完全反应组的SIRT3表达水平。使用 STRING 数据库构建了蛋白质-蛋白质相互作用网络。进行基因组富集分析（GSEA）以探索SIRT3的潜在功能：结果：利用三个独立队列对SIRTs的表达和BC的OS进行了系统分析：结果：通过使用三个独立队列：TCGA-BRCA、METABRIC和GSE16446对SIRTs表达和BC的OS进行系统分析，我们发现在TCGA-BRCA队列中，SIRT3的高表达与TNBC较差的OS显著相关，这在METABRIC和GSE16446队列中得到了验证。SIRT3的表达与BC亚型和美国癌症联合委员会（AJCC）T分期相关，但与诊断年龄、种族或肿瘤分期无关。此外，SIRT3表达较高的TNBC患者在新辅助化疗后的pCR率较低（p = 6.40e-03），而在TNBC患者中，pCR组的SIRT3表达明显低于非pCR组（p = 4.2e-03）。GSEA表明，SIRT3参与了药物相关通路，如氧化磷酸化、细胞色素P450对异种生物的代谢和药物代谢：我们的研究表明，SIRT3是TNBC患者OS和新辅助化疗敏感性的潜在生物标志物。结论：我们的研究表明，SIRT3是TNBC患者OS和新辅助化疗敏感性的潜在生物标志物，也有助于为TNBC患者选择合适的候选者和治疗方案。

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来源期刊

Cancer Management and Research Medicine-Oncology

CiteScore

7.40

自引率

0.00%

发文量

448

审稿时长

16 weeks

期刊介绍： Cancer Management and Research is an international, peer reviewed, open access journal focusing on cancer research and the optimal use of preventative and integrated treatment interventions to achieve improved outcomes, enhanced survival, and quality of life for cancer patients. Specific topics covered in the journal include: ◦Epidemiology, detection and screening ◦Cellular research and biomarkers ◦Identification of biotargets and agents with novel mechanisms of action ◦Optimal clinical use of existing anticancer agents, including combination therapies ◦Radiation and surgery ◦Palliative care ◦Patient adherence, quality of life, satisfaction The journal welcomes submitted papers covering original research, basic science, clinical & epidemiological studies, reviews & evaluations, guidelines, expert opinion and commentary, and case series that shed novel insights on a disease or disease subtype.