Prostaglandin D2 expression is prognostic in high‑grade serous ovarian cancer

  • Authors:
    • Mariana Rezende Alves
    • Nayra Soares Do Amaral
    • Fabio Albuquerque Marchi
    • Felipe Ilelis De Barros Silva
    • Alexandre André Balieiro Anastácio Da Costa
    • Kátia Cândido Carvalho
    • Glauco Baiocchi
    • Fernando Augusto Soares
    • Louise De Brot
    • Rafael Malagoli Rocha
  • View Affiliations

  • Published online on: January 28, 2019     https://doi.org/10.3892/or.2019.6984
  • Pages: 2254-2264
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Abstract

To identify biomarkers that could predict response or lack of response to conventional chemotherapy at the time of diagnosis of high‑grade serous ovarian carcinoma (HGSOC), the present study compared large‑scale gene expression from patients with short or long disease‑free survival times, according to the last cycle of chemotherapy, and validated these findings using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and conventional immunohistochemical (IHC) analysis. Samples were selected for microarray evaluation, at the time of diagnosis, using the following criteria: Identical debulking primary surgery, International Federation of Gynaecology and Obstetrics staging, histological subtype and grade. These were divided into 2 groups, regarding the outcome after 2 years of follow-up. Prostaglandin D2 synthase 21 kDa (brain) (PTGDS) was found to be expressed at a significantly higher level in the tumours of patients with a short disease‑free survival time, and this was validated by RT‑qPCR in all samples. Furthermore, the study evaluated PGD2, the protein product of the PTGDS gene, in a large cohort of 114 HGSOC patients using the Ventana Benchmark automated platform, and IHC positivity was correlated with clinicopathological data and outcome. The global gene expression analysis identified 1,149 genes that were differentially expressed in microarray data, according to the patient outcome. Further analysis RT‑qPCR validated PTGDS gene expression in the same samples (r=0.945; P<0.001). IHC analysis showed an inverse profile, with positivity for PGD2 strongly associated with an increase in disease‑free survival (P=0.009), the absence of relapse (P=0.039) and sensitivity to platinum‑based therapy (P=0.016). Multiple Cox regression showed that IHC evaluation of PGD2 was also a prognostic marker associated with relapse (hazard ratio, 0.37; P=0.002). Overall, the results showed that IHC evaluation of PGD2 is an independent marker of good prognosis in HGSOC. This finding contributes to our understanding of the mechanism of tumour regulation and to investigations into biomarkers that predict response to chemotherapy.

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APA
Alves, M.R., Do Amaral, N.S., Marchi, F.A., Silva, F.I., Da Costa, A.A., Carvalho, K.C. ... Rocha, R.M. (2019). Prostaglandin D2 expression is prognostic in high‑grade serous ovarian cancer. Oncology Reports, 41, 2254-2264. https://doi.org/10.3892/or.2019.6984
MLA
Alves, M. R., Do Amaral, N. S., Marchi, F. A., Silva, F. I., Da Costa, A. A., Carvalho, K. C., Baiocchi, G., Soares, F. A., De Brot, L., Rocha, R. M."Prostaglandin D2 expression is prognostic in high‑grade serous ovarian cancer". Oncology Reports 41.4 (2019): 2254-2264.
Chicago
Alves, M. R., Do Amaral, N. S., Marchi, F. A., Silva, F. I., Da Costa, A. A., Carvalho, K. C., Baiocchi, G., Soares, F. A., De Brot, L., Rocha, R. M."Prostaglandin D2 expression is prognostic in high‑grade serous ovarian cancer". Oncology Reports 41, no. 4 (2019): 2254-2264. https://doi.org/10.3892/or.2019.6984