Abstract
Alterations in mitochondrial DNA (mtDNA) have been implicated in carcinogenesis and tumor progression. We here evaluated the diagnostic and prognostic potential of mtDNA as a biomarker for breast cancer. Using multiplex real-time polymerase chain reaction, nuclear DNA (nDNA) and mtDNA levels in serum, buffy coat, tumor, and tumor-adjacent tissue samples from 50 breast cancer patients were determined and assessed for associations with clinicopathological features. To evaluate mtDNA as a biomarker for distinguishing between the four sample types, we created receiver operating characteristic (ROC) curves. The mtDNA levels in buffy coat were significantly lower than in other sample types. Relative to tumor-adjacent tissue, reduced levels of mtDNA were identified in buffy coat and tumor tissue but not in serum. According to ROC curve analysis, mtDNA levels could be used to distinguish between buffy coat and tumor-adjacent tissue samples with good sensitivity (77%) and specificity (83%). Moreover, mtDNA levels in serum and tumor tissue were positively associated with cancer TMN stage. The mtDNA levels in blood samples may represent a promising, non-invasive biomarker in breast cancer patients. Additional, large-scale validation studies are required to establish the potential use of mtDNA levels in the early diagnosis and monitoring of breast cancer.
Highlights
Breast cancer is one of the most common cancers and a leading cause of cancer death in women
0.077 and rs = 0.342, P = 0.017, respectively). These results suggest that the relationship between nDNA and mitochondrial DNA (mtDNA) in serum and tumor tissue from breast cancer patients is different from that present in buffy coat and tumor-adjacent breast tissue
Our data revealed that (1) mtDNA levels in matched serum, buffy coat, tumor tissue, and tumor-adjacent tissue were significantly different and (2) mtDNA levels in serum and tumor tissue were associated with the clinical stages of breast cancer
Summary
Breast cancer is one of the most common cancers and a leading cause of cancer death in women. Tumor biomarkers for the early diagnosis of breast cancer have not yet been validated or incorporated into oncology practice (Radpour et al, 2009). In light of the promise of using circulating DNA as a non-invasive marker for cancer assessment, changes in blood mtDNA may serve as a sensitive, early biomarker for the non-invasive detection of tumors (Fliss et al, 2000; Radpour et al, 2009; Yu, 2011; GonzalezMasia et al, 2013). We measured mtDNA levels in these samples and investigated associations with clinicopathological characteristics. These findings extend our understanding of the role of mtDNA alterations in breast cancer pathogenesis
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