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Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer.

Xia P, An HX, Dang CX, Radpour R, Kohler C, Fokas E, Engenhart-Cabillic R, Holzgreve W, Zhong XY - BMC Cancer (2009)

Bottom Line: The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023).Early detection of breast cancer has proved difficult and current detection methods are inadequate.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.

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Affiliation: Department of Surgical Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061 Xi'an, PR China. xiapeng30000@yahoo.com.cn

ABSTRACT

Background: Alterations 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.

Methods: Peripheral 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.

Results: The 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.

Conclusion: Early 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.

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Correlation of nDNA content and mtDNA content in peripheral blood in normal group. Scatter plot illustrates the Ct values of GAPDH amplicon (X axis) against the Ct values of MTATP 8 amplicon (Y axis) in blood samples of normal group (n = 50). The correlation rate is highly significant (p = 0.0001) according the Spearman' rho test.
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Figure 1: Correlation of nDNA content and mtDNA content in peripheral blood in normal group. Scatter plot illustrates the Ct values of GAPDH amplicon (X axis) against the Ct values of MTATP 8 amplicon (Y axis) in blood samples of normal group (n = 50). The correlation rate is highly significant (p = 0.0001) according the Spearman' rho test.

Mentions: The average Ct values of GAPDH amplicon in the normal group were correlated with those of MTATP8 gene amplicon (Spearman's rho Test: p < 0.001, r = 0.496) (Figure 1). In contrast, no significant correlation was detected in cancerous group (p > 0.05, r = 0.148) (Figure 2), suggesting an alteration of the relationship between nDNA and mtDNA in blood samples of breast cancer patients.


Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer.

Xia P, An HX, Dang CX, Radpour R, Kohler C, Fokas E, Engenhart-Cabillic R, Holzgreve W, Zhong XY - BMC Cancer (2009)

Correlation of nDNA content and mtDNA content in peripheral blood in normal group. Scatter plot illustrates the Ct values of GAPDH amplicon (X axis) against the Ct values of MTATP 8 amplicon (Y axis) in blood samples of normal group (n = 50). The correlation rate is highly significant (p = 0.0001) according the Spearman' rho test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2803198&req=5

Figure 1: Correlation of nDNA content and mtDNA content in peripheral blood in normal group. Scatter plot illustrates the Ct values of GAPDH amplicon (X axis) against the Ct values of MTATP 8 amplicon (Y axis) in blood samples of normal group (n = 50). The correlation rate is highly significant (p = 0.0001) according the Spearman' rho test.
Mentions: The average Ct values of GAPDH amplicon in the normal group were correlated with those of MTATP8 gene amplicon (Spearman's rho Test: p < 0.001, r = 0.496) (Figure 1). In contrast, no significant correlation was detected in cancerous group (p > 0.05, r = 0.148) (Figure 2), suggesting an alteration of the relationship between nDNA and mtDNA in blood samples of breast cancer patients.

Bottom Line: The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023).Early detection of breast cancer has proved difficult and current detection methods are inadequate.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Surgical Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, 710061 Xi'an, PR China. xiapeng30000@yahoo.com.cn

ABSTRACT

Background: Alterations 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.

Methods: Peripheral 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.

Results: The 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.

Conclusion: Early 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.

Show MeSH
Related in: MedlinePlus