Department of Breast Surgery, Fujian Medical University Union Hospital, No.29, Xin Quan Road, Gulou District, Fuzhou, 350001, Fujian Province, China.
Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian Province, China.
BMC Cancer. 2023 Apr 25;23(1):377. doi: 10.1186/s12885-023-10838-x.
Compelling evidence has indicated a significant association between leukocyte mitochondrial DNA copy number (mtDNAcn) and prognosis of several malignancies in a cancer-specific manner. However, whether leukocyte mtDNAcn can predict the clinical outcome of breast cancer (BC) patients has not been well investigated.
The mtDNA copy number of peripheral blood leukocytes from 661 BC patients was measured using a Multiplex AccuCopy™Kit based on a multiplex fluorescence competitive PCR principle. Kaplan-Meier curves and Cox proportional hazards regression model were applied to investigate the association of mtDNAcn with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer special survival (BCSS), and overall survival (OS) of patients. The possible mtDNAcn-environment interactions were also evaluated by the Cox proportional hazard regression models.
BC patients with higher leukocyte mtDNA-CN exhibited a significantly worse iDFS than those with lower leukocyte mtDNAcn (5-year iDFS: fully-adjusted model: HR = 1.433[95%CI 1.038-1.978], P = 0.028). Interaction analyses showed that mtDNAcn was significantly associated with hormone receptor status (adjusted p for interaction: 5-year BCSS: 0.028, 5-year OS: 0.022), so further analysis was mainly in the HR subgroup. Multivariate Cox regression analysis demonstrated that mtDNAcn was an independent prognostic factor for both BCSS and OS in HR-positive patients (HR+: 5-year BCSS: adjusted HR (aHR) = 2.340[95% CI 1.163-4.708], P = 0.017 and 5-year OS: aHR = 2.446 [95% CI 1.218-4.913], P = 0.011).
For the first time, our study demonstrated that leukocyte mtDNA copy number might influence the outcome of early-stage breast cancer patients depending on intrinsic tumor subtypes in Chinese women.
大量证据表明，白细胞线粒体 DNA 拷贝数（mtDNAcn）与多种癌症的预后存在显著关联，且这种关联具有癌症特异性。然而，白细胞 mtDNAcn 是否可以预测乳腺癌（BC）患者的临床结局尚未得到充分研究。
采用基于多重荧光竞争 PCR 原理的 Multiplex AccuCopy™Kit 检测 661 例 BC 患者外周血白细胞的 mtDNA 拷贝数。Kaplan-Meier 曲线和 Cox 比例风险回归模型用于探讨 mtDNAcn 与浸润性无病生存期（iDFS）、远处无病生存期（DDFS）、乳腺癌特异性生存期（BCSS）和总生存期（OS）的相关性。还通过 Cox 比例风险回归模型评估了可能的 mtDNAcn-环境相互作用。
白细胞 mtDNA-CN 较高的 BC 患者的 iDFS 明显差于白细胞 mtDNAcn 较低的患者（5 年 iDFS：完全调整模型：HR=1.433[95%CI 1.038-1.978]，P=0.028）。交互分析表明，mtDNAcn 与激素受体状态显著相关（调整后的交互作用 P 值：5 年 BCSS：0.028，5 年 OS：0.022），因此进一步的分析主要在 HR 亚组中进行。多变量 Cox 回归分析表明，mtDNAcn 是 HR 阳性患者 BCSS 和 OS 的独立预后因素（HR+：5 年 BCSS：调整后的 HR（aHR）=2.340[95%CI 1.163-4.708]，P=0.017 和 5 年 OS：aHR=2.446 [95%CI 1.218-4.913]，P=0.011）。
本研究首次表明，白细胞 mtDNA 拷贝数可能会影响中国女性早期乳腺癌患者的结局，这取决于内在的肿瘤亚型。
