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Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases.

Joosse SA, Müller V, Steinbach B, Pantel K, Schwarzenbach H - Br. J. Cancer (2014)

Bottom Line: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001).In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001).Moreover, serum miR-202 is associated with prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT

Background: MAGE-A (melanoma-associated antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS.

Methods: To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years.

Results: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1.

Conclusions: Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis.

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Related in: MedlinePlus

Circulating MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in breast cancer patients, patients with benign breast disease and healthy women. Box plots showing the different amounts of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 that circulate in the blood of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients (n=102, A). As determined by ANOVA, the P-values of the statistical evaluations are indicated for the comparisons of healthy women vs patients with benign disease, healthy women vs breast cancer patients and patients with benign disease vs breast cancer patients (B).
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fig1: Circulating MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in breast cancer patients, patients with benign breast disease and healthy women. Box plots showing the different amounts of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 that circulate in the blood of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients (n=102, A). As determined by ANOVA, the P-values of the statistical evaluations are indicated for the comparisons of healthy women vs patients with benign disease, healthy women vs breast cancer patients and patients with benign disease vs breast cancer patients (B).

Mentions: Cell-free RNA extracted from blood serum of 102 breast cancer patients, as well as from 26 patients with benign breast disease and 37 healthy women was measured by quantitative real-time PCR. As shown in the box plot of Figure 1, the serum levels of MAGE-A1 (P<0.001), MAGE-A2 (P<0.001), MAGE-A3 (P<0.001) and BORIS RNA (P<0.001) were significantly higher in breast cancer patients than in healthy women. Although the levels of MAGE-A1 (P=0.043), MAGE-A2 (P=0.020) and BORIS (P<0.001) were also elevated in patients with benign disease compared with healthy women, there was a further significant increase in breast cancer patients. Thus, the serum levels of MAGE-A1 (P<0.001), MAGE-A2 (P<0.001), MAGE-A3 (P=0.003) and BORIS RNA (P=0.020) could significantly differentiate between benign and malignant breast tumours. In contrast, the serum levels of MAGE-A12 RNA were similar in the three cohorts (Figure 1).


Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases.

Joosse SA, Müller V, Steinbach B, Pantel K, Schwarzenbach H - Br. J. Cancer (2014)

Circulating MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in breast cancer patients, patients with benign breast disease and healthy women. Box plots showing the different amounts of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 that circulate in the blood of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients (n=102, A). As determined by ANOVA, the P-values of the statistical evaluations are indicated for the comparisons of healthy women vs patients with benign disease, healthy women vs breast cancer patients and patients with benign disease vs breast cancer patients (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150270&req=5

fig1: Circulating MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in breast cancer patients, patients with benign breast disease and healthy women. Box plots showing the different amounts of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 that circulate in the blood of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients (n=102, A). As determined by ANOVA, the P-values of the statistical evaluations are indicated for the comparisons of healthy women vs patients with benign disease, healthy women vs breast cancer patients and patients with benign disease vs breast cancer patients (B).
Mentions: Cell-free RNA extracted from blood serum of 102 breast cancer patients, as well as from 26 patients with benign breast disease and 37 healthy women was measured by quantitative real-time PCR. As shown in the box plot of Figure 1, the serum levels of MAGE-A1 (P<0.001), MAGE-A2 (P<0.001), MAGE-A3 (P<0.001) and BORIS RNA (P<0.001) were significantly higher in breast cancer patients than in healthy women. Although the levels of MAGE-A1 (P=0.043), MAGE-A2 (P=0.020) and BORIS (P<0.001) were also elevated in patients with benign disease compared with healthy women, there was a further significant increase in breast cancer patients. Thus, the serum levels of MAGE-A1 (P<0.001), MAGE-A2 (P<0.001), MAGE-A3 (P=0.003) and BORIS RNA (P=0.020) could significantly differentiate between benign and malignant breast tumours. In contrast, the serum levels of MAGE-A12 RNA were similar in the three cohorts (Figure 1).

Bottom Line: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001).In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001).Moreover, serum miR-202 is associated with prognosis.

View Article: PubMed Central - PubMed

Affiliation: Department of Tumor Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

ABSTRACT

Background: MAGE-A (melanoma-associated antigen-A) are promising targets for specific immunotherapy and their expression may be induced by the epigenetic factor BORIS.

Methods: To determine their relevance for breast cancer, we quantified the levels of MAGE-A1, -A2, -A3, -A12 and BORIS mRNA, as well as microRNAs let-7b and miR-202 in pre- and postoperative serum of 102 and 34 breast cancer patients, respectively, and in serum of 26 patients with benign breast diseases and 37 healthy women by real-time PCR. The mean follow-up time of the cancer patients was 6.2 years.

Results: The serum levels of MAGE-A and BORIS mRNA, as well as let-7b were significantly higher in patients with invasive carcinomas than in patients with benign breast diseases or healthy women (P<0.001), whereas the levels of miR-202 were elevated in both patient cohorts (P<0.001). In uni- and multivariate analyses, high levels of miR-202 significantly correlated with poor overall survival (P=0.0001). Transfection of breast cancer cells with synthetic microRNAs and their inhibitors showed that let-7b and miR-202 did not affect the protein expression of MAGE-A1.

Conclusions: Based on their cancer-specific increase in breast cancer patients, circulating MAGE-A and BORIS mRNAs may be further explored for early detection of breast cancer and monitoring of MAGE-directed immunotherapies. Moreover, serum miR-202 is associated with prognosis.

Show MeSH
Related in: MedlinePlus