Abstract
BackgroundAlterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA). We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters.MethodsPeripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu protein.ResultsThe content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023). Reduced mtDNA was found often in post menopausal cancer group (P = 0.024). No difference in mtDNA content, in regards to age (p = 0.564), lymph node involvement (p = 0.673), ER (p = 0.877), PR (p = 0.763), and Her-2/neu expression (p = 0.335), was observed.ConclusionEarly detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.
Highlights
IntroductionAlterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis
Alterations of mitochondrial DNA have been implicated in carcinogenesis
MtDNA alterations are correlated with various cancer types, suggesting that the mitochondrial genome may be a critical contributing factor in carcinogenesis. mitochondrial DNA (mtDNA) content has been implicated as a potential biomarker for several cancer types [5]
Summary
Alterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. In patients with mitochondrial disease, mitochondrial function is vulnerable to damages due to deletions, mutations or replication abnormalities of mitochondrial DNA (mtDNA) resulting in energy depletion and increased susceptibility to apoptosis [4]. MtDNA alterations are correlated with various cancer types, suggesting that the mitochondrial genome may be a critical contributing factor in carcinogenesis. MtDNA content has been implicated as a potential biomarker for several cancer types [5]. Several studies have revealed an increased mtDNA content in prostate [14], untreated head and neck [15], thyroid [5], endometrial [16], and pancreatic cancer [17]. MtDNA alterations were detected in bodily fluids, suggesting that mtDNA changes might serve as sensitive early biomarker for non-invasive detection of several types of solid cancer including breast cancer [18]
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