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. 2023 Apr 25;23(1):377.
doi: 10.1186/s12885-023-10838-x.

High leukocyte mitochondrial DNA copy number contributes to poor prognosis in breast cancer patients

Wenzhe Zhang  1   2   3 , Songping Lin  4 , Bangwei Zeng  5 , Xiaobin Chen  1   2   3 , Lili Chen  1   2   3 , Minyan Chen  1   2   3 , Wenhui Guo  1   2   3 , Yuxiang Lin  1   2   3 , Liuwen Yu  1   2   3 , Jialin Hou  1   2   3 , Yan Li  1   2   3 , Shengmei Li  1   2   3 , Xuan Jin  1   2   3 , Weifeng Cai  1   2   3 , Kun Zhang  1   2   3 , Qian Nie  1   2   3 , Hanxi Chen  1   2   3 , Jing Li  1   2   3 , Peng He  1   2   3 , Qindong Cai  1   2   3 , Yibin Qiu  1   2   3 , Chuan Wang  6   7   8 , Fangmeng Fu  9   10   11
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High leukocyte mitochondrial DNA copy number contributes to poor prognosis in breast cancer patients

Wenzhe Zhang et al. BMC Cancer. .

Abstract

Background: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Breast cancer; Leukocyte; Mitochondrial DNA copy number; Survival.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
Kaplan-Meier curves for iDFS (a), DDFS (b), BCSS (c), and OS (d) due to BC by Quintile 2–5 AND Quintile 1 of mitochondrial DNA copy number. Abbreviations: iDFS, invasive disease-free survival; DDFS, distant disease-free survival; BCSS, BC special survival; OS, overall survival
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