Analysis of mitochondrial DNA copy number variation in blood and tissue samples of metastatic breast cancer patients (A pilot study)

Kumar, Neeraj; Panjwani, Ghanish; Ghosh, Ashok; Haque, Rizwanul; Sharma, Lokendra

doi:10.1016/j.bbrep.2021.100931

Cited by 9 publications

(7 citation statements)

References 26 publications

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“…In contrast to the observation of mtDNAcn reduction in breast tumor tissues, the studies of leukocyte mtDNAcn of breast cancer patients and its association with prognosis have been heterogeneous. Rai et al showed an inverse relation in blood vs. tissue samples in breast cancer patients [33]. Our results were consistent with a meta-analysis that summarized the results of 18 studies involving 3961 cancer patients and concluded that elevated mtDNAcns in peripheral blood leukocytes and tumor tissues predict the opposite outcome of cancer [34].…”

Section: Discussionsupporting

confidence: 91%

Subtype-Specific Associations Between leukocyte mtDNA Copy Number and the Survival of Early-Sage Breast Cancer

Zhang

Lin

Zeng

et al. 2022

Preprint

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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: Breast cancer (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 that 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.

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Section: Discussionsupporting

confidence: 91%

Subtype-Specific Associations Between leukocyte mtDNA Copy Number and the Survival of Early-Sage Breast Cancer

Zhang

Lin

Zeng

et al. 2022

Preprint

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“…The existence of fluctuation of copy number of mtDNA was previously reported in relation to injury and oxidative stress that contribute to the development of the toxicity of dioxin-like compounds [ 47 ] in acute myeloid leukemia (higher in aggressiveness stages) [ 48 ], hepatocellular [ 49 ], or tissue samples in breast cancer [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Arance

Ramírez

Rubio-Roldán

et al. 2021

Cancers

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Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

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“…Several studies of breast cancer have shown specific mutations in mtDNA [50] and lower MCN [51][52][53][54], but the significance of these alterations is not completely understood. In contrast, other studies have associated breast cancer with higher MCN [55,56]. Thus, MCN most likely relates to the molecular subtype of breast cancer, as well as the level of progression, epithelial-mesenchymal transition, metastasis, and therapeutic resistance [57][58][59].…”

Section: Discussionmentioning

confidence: 91%

Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue

Zakic,

Kalezic,

Drvendzija

et al. 2024

Cells

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The close cooperation between breast cancer and cancer-associated adipose tissue (CAAT) shapes the malignant phenotype, but the role of mitochondrial metabolic reprogramming and obesity in breast cancer remains undecided, especially in premenopausal women. Here, we examined mitochondrial metabolic dynamics in paired biopsies of malignant versus benign breast tumor tissue and CAAT in normal-weight and overweight/obese premenopausal women. Lower protein level of pyruvate dehydrogenase and citrate synthase in malignant tumor tissue indicated decreased carbon flux from glucose into the Krebs cycle, whereas the trend was just the opposite in malignant CAAT. Simultaneously, stimulated lipolysis in CAAT of obese women was followed by upregulated β-oxidation, as well as fatty acid synthesis enzymes in both tumor tissue and CAAT of women with malignant tumors, corroborating their physical association. Further, protein level of electron transport chain complexes was generally increased in tumor tissue and CAAT from women with malignant tumors, respective to obesity. Preserved mitochondrial structure in malignant tumor tissue was also observed. However, mitochondrial DNA copy number and protein levels of PGC-1α were dependent on both malignancy and obesity in tumor tissue and CAAT. In conclusion, metabolic cooperation between breast cancer and CAAT in premenopausal women involves obesity-related, synchronized changes in mitochondrial metabolism.

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Analysis of mitochondrial DNA copy number variation in blood and tissue samples of metastatic breast cancer patients (A pilot study)

Cited by 9 publications

References 26 publications

Subtype-Specific Associations Between leukocyte mtDNA Copy Number and the Survival of Early-Sage Breast Cancer

Subtype-Specific Associations Between leukocyte mtDNA Copy Number and the Survival of Early-Sage Breast Cancer

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness

Breast Cancer: Mitochondria-Centered Metabolic Alterations in Tumor and Associated Adipose Tissue

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