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Systematic analysis and validation of differential gene expression in ovarian serous adenocarcinomas and normal ovary

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Abstract

Purpose

Cancer of the ovary confers the worst prognosis among women with gynecological malignancies, primarily because most ovarian cancers are diagnosed at late stage. Hence, there is a substantial need to develop new diagnostic biomarkers to enable detection of ovarian cancer at earlier stages, which would confer better prognosis. In addition, the identification of druggable targets is of substantial interest to find new therapeutic strategies for ovarian cancer.

Methods

The expression of 22,500 genes in a series of 67 serous papillary carcinomas was compared with 9 crudely enriched normal ovarian tissue samples by RNA hybridization on oligonucleotide microarrays. Multiple genes with near-uniformly expression were elevated in carcinomas of varying grade and malignant potential, including several previously described genes (e.g., MUC-1, CD9, CD24, claudin 3, and mesothelin). We performed immunohistochemical staining with antibodies against several of the proteins encoded by differentially expressed genes in an independent cohort of 71 cases of paraffin-embedded ovarian cancer samples.

Results

We found striking differences in EpCAM (p < 0.005), CD9 (p < 0.001), MUC-1 (p < 0.001), and claudin 3 proteins (p < 0.001) but not for mesothelin (p > 0.05) using the Mann–Whitney U test.

Conclusions

Protein expression of a majority of the differentially expressed genes tested was found to be elevated in ovarian carcinomas and, as such, define potential new biomarkers or targets.

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Acknowledgments

We thank Lisa Sapinoso for preparing the gene array analyses. We also thank Herta Bettendorf for her excellent staining of the tissue microarrays. This work was partially supported by Deutsche Krebshilfe/German Cancer Aid grant 70-3099-Me1 and by NCI-grant 5R21CA152794-02. We thank Ulrike Schulz at MediStat for her excellent support in preparing statistical analyses.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gynecology and Obstetrics, University Medical Center RWTH, Pauwelsstrasse 30, 52074, Aachen, Germany

    Dirk Bauerschlag, Karen Bräutigam, Nicolai Maass & Ivo Meinhold-Heerlein

  2. Department of Pathology, University of Marburg, Marburg, Baldingerstraße, 35043, Marburg, Germany

    Roland Moll

  3. Department of Gynecology and Obstetrics, University Medical Center Charite Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Jalid Sehouli

  4. Department of Gynecology and Obstetrics, University Medical Center Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany

    Alexander Mustea

  5. Department of Gynecology and Obstetrics, Helios Hospital Krefeld, Lutherplatz 40, 47805, Krefeld, Germany

    Darius Salehin

  6. Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA, 92037, USA

    Maryla Krajewska & John C. Reed

  7. Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA

    Garret M. Hampton

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  1. Dirk Bauerschlag
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  2. Karen Bräutigam
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  11. Ivo Meinhold-Heerlein
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Corresponding author

Correspondence to Dirk Bauerschlag.

Additional information

Dirk Bauerschlag and Karen Bräutigam equally contributed to this work.

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Bauerschlag, D., Bräutigam, K., Moll, R. et al. Systematic analysis and validation of differential gene expression in ovarian serous adenocarcinomas and normal ovary. J Cancer Res Clin Oncol 139, 347–355 (2013). https://doi.org/10.1007/s00432-012-1334-8

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  • DOI: https://doi.org/10.1007/s00432-012-1334-8

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