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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

Serum levels of RNA and miRs in breast cancer patients before and after surgery. Box plots showing the comparison of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in serum of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients before (n=34) and after surgery (n=34, A). As determined by ANOVA, the mean differences and adjusted P-values of the statistical evaluations are indicated (B).
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fig2: Serum levels of RNA and miRs in breast cancer patients before and after surgery. Box plots showing the comparison of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in serum of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients before (n=34) and after surgery (n=34, A). As determined by ANOVA, the mean differences and adjusted P-values of the statistical evaluations are indicated (B).

Mentions: Although the serum levels of MAGE-A2 and MAGE-A3 RNA decreased postoperatively, the decrease was not significant. However, significant lower levels of MAGE-A1 and BORIS RNA could be observed (P<0.001, Figure 2) after surgery. In contrast, the serum levels of miR-202 were significantly higher in breast cancer patients after surgery than in patients before surgery (P<0.001, Figure 2).


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)

Serum levels of RNA and miRs in breast cancer patients before and after surgery. Box plots showing the comparison of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in serum of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients before (n=34) and after surgery (n=34, A). As determined by ANOVA, the mean differences and adjusted P-values of the statistical evaluations are indicated (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Serum levels of RNA and miRs in breast cancer patients before and after surgery. Box plots showing the comparison of MAGE-A1, -A2, -A3, -A12 and BORIS RNA, and let-7b and miR-202 levels in serum of healthy individuals (n=37), patients with benign breast disease (n=26) and breast cancer patients before (n=34) and after surgery (n=34, A). As determined by ANOVA, the mean differences and adjusted P-values of the statistical evaluations are indicated (B).
Mentions: Although the serum levels of MAGE-A2 and MAGE-A3 RNA decreased postoperatively, the decrease was not significant. However, significant lower levels of MAGE-A1 and BORIS RNA could be observed (P<0.001, Figure 2) after surgery. In contrast, the serum levels of miR-202 were significantly higher in breast cancer patients after surgery than in patients before surgery (P<0.001, Figure 2).

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