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Expression and clinical role of the dipeptidyl peptidases DPP8 and DPP9 in ovarian carcinoma

Virchows Archiv volume 474, pages 177–185 (2019)Cite this article

Abstract

Dipeptidyl peptidase 9 (DPP9) was recently identified as fusion gene in ovarian high-grade serous carcinoma (HGSC). The aim of this study was to analyze the expression and clinical relevance of DPP8 and DPP9 in ovarian carcinoma, with focus on HGSC. mRNA expression by qRT-PCR of DPP8 and DPP9 was analyzed in 232 carcinomas, including 114 effusions and 118 surgical specimens (89 ovarian, 29 solid metastases). DPP8 and DPP9 protein expression was analyzed in 92 effusions. DPP8 and DPP9 mRNA was overexpressed in effusions compared to solid lesions in analysis of all histotypes (p < 0.001 both), as well as in analysis limited to HGSC (p < 0.001 for DPP9, p = 0.002 for DPP8). DPP9 mRNA was additionally overexpressed in HGSC compared to other histotypes (p = 0.021). DPP8 and DPP9 protein was expressed in carcinoma cells in 31/92 (37%) and 81/92 (88%) effusions, respectively. DPP8 protein expression in HGSC effusions was significantly related to better (complete) chemoresponse at diagnosis (p = 0.005). DPP8 and DPP9 mRNA and protein expression was unrelated to survival in analysis of the entire effusion cohort. However, higher DPP9 mRNA levels were significantly related to longer overall survival in pre-chemotherapy effusions (p = 0.049). In conclusion, DPP8 and DPP9 mRNA is frequently expressed in ovarian carcinoma, whereas DPP9 is more frequently expressed at the protein level. DPP8 and DPP9 may be related to less aggressive disease in advanced-stage HGSC.

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Funding

This work was supported by The Inger and John Fredriksen Foundation for Ovarian Cancer Research. Marta Brunetti is supported by a grant from the South-East Health Region of Norway.

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Affiliations

  1. Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310, Oslo, Norway

    Marta Brunetti, Arild Holth & Ben Davidson

  2. Section for Cancer Cytogenetics, Institute for Cancer Genetics and Informatics, Norwegian Radium Hospital, Oslo University Hospital, N-0310, Oslo, Norway

    Marta Brunetti, Ioannis Panagopoulos & Francesca Micci

  3. Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, N-0316, Oslo, Norway

    Marta Brunetti, Anne Cathrine Staff & Ben Davidson

  4. Division of Obstetrics and Gynecology, Ullevål University Hospital, N-0407, Oslo, Norway

    Anne Cathrine Staff

Authors
  1. Marta Brunetti
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  2. Arild Holth
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  3. Ioannis Panagopoulos
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  4. Anne Cathrine Staff
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  5. Francesca Micci
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  6. Ben Davidson
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Contributions

MB performed the PCR experiments and wrote the manuscript.

AH performed the IHC experiments.

IP participated in performing the PCR experiments and critically read the manuscript.

ACS provided clinical data and specimens and critically read the manuscript.

FM designed the study, supervised the PCR experiments, and critically read the manuscript.

BD designed the study, performed the statistical analysis, scored the immunostains, and supervised the writing of the manuscript.

Corresponding author

Correspondence to Ben Davidson.

Ethics declarations

The study was approved by the Regional Committee for Medical Research Ethics in Norway.

Conflict of interest

The authors declare that they have no conflict of interest.

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Brunetti, M., Holth, A., Panagopoulos, I. et al. Expression and clinical role of the dipeptidyl peptidases DPP8 and DPP9 in ovarian carcinoma. Virchows Arch 474, 177–185 (2019). https://doi.org/10.1007/s00428-018-2487-x

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  • DOI: https://doi.org/10.1007/s00428-018-2487-x

Keywords

  • Ovarian carcinoma
  • Dipeptidyl peptidases
  • Disease progression
  • Survival
  • Immunohistochemistry
  • Quantitative PCR