Research Papers:

Improved sensitivity for detection of breast cancer by combination of miR-34a and tumor markers CA 15-3 or CEA

Martin Zaleski, Makbule Kobilay, Lars Schroeder, Manuel Debald, Alexander Semaan, Karina Hettwer, Steffen Uhlig, Walther Kuhn, Gunther Hartmann and Stefan Holdenrieder _

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Oncotarget. 2018; 9:22523-22536. https://doi.org/10.18632/oncotarget.25077

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Martin Zaleski1, Makbule Kobilay1, Lars Schroeder2,3, Manuel Debald2,3, Alexander Semaan4, Karina Hettwer5,6, Steffen Uhlig5,6, Walther Kuhn2,3, Gunther Hartmann1,3 and Stefan Holdenrieder1,3,6

1Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany

2Department of Gynecology and Obstetrics, University Hospital Bonn, Bonn, Germany

3Center for Integrated Oncology (CIO) Köln/Bonn, Bonn, Germany

4Department of Surgery, University Hospital Bonn, Bonn, Germany

5QuoData Statistics, Dresden, Germany

6Joint Research and Services Center for Biomarker Evaluation in Oncology, Bonn/Dresden, Germany

Correspondence to:

Stefan Holdenrieder, email: [email protected]

Keywords: breast cancer; miRNA; miR-34a; CEA; CA 15-3

Received: October 03, 2017     Accepted: March 02, 2018     Published: April 27, 2018


Background: MicroRNAs biomarkers have shown value for diagnosis and prognosis of various cancers. Combination with established tumor markers has rarely been done.

Results: Breast cancer patients had significantly higher serum RNA loads (AUC 0.665), lower miR-34a (AUC 0.772), higher CEA and CA 15-3 levels (AUCs 0.717 and 0.721) than healthy controls. miR-34a correlated with tumor stage and hormone receptor status. There was no significant difference between groups for all other miRNAs. Combination of miR-34a with CEA or CA 15-3 led to improved AUCs of 0.844 and 0.800, respectively. Sensitivity of miR-34a and CA 15-3 reached 56.1% at 95% specificity. When compared with benign breast diseases, combination of miR-34a (AUC 0.719) and CEA (0.623) or CA 15-3 (0.619) resulted in improved performances (0.794 and 0.741). Sensitivity of miR-34a and CA 15-3 reached 53.7% at 95% specificity.

Conclusion: While miR-34a provides valuable information for diagnosis and staging, combination with tumor markers CA15-3 or CEA improves the sensitivity for breast cancer detection.

Patients and Methods: The diagnostic relevance of the miR-21, miR-34a, miR-92a, miR-155, miR-222 and miR-let-7c was tested in sera of 103 individuals (55 breast cancer, 20 benign breast diseases, 28 healthy controls). MiRNAs were detected by quantitative rt-PCR after extraction and reverse transcription. Cel-miR-39 and miR-16 were used for normalization. Established tumor markers CEA, CA 15-3, CA 19-9 and CA 125 were measured by automatized immunoassays. Diagnostic performance was tested by areas under the curve (AUC) of receiver operating characteristic (ROC) curves and sensitivities at 90% and 95% specificity.

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