Oncotarget

Research Papers:

The putative oncogene, CRNDE, is a negative prognostic factor in ovarian cancer patients

Lukasz Michal Szafron _, Anna Balcerak, Ewa Anna Grzybowska, Barbara Pienkowska-Grela, Agnieszka Podgorska, Renata Zub, Magdalena Olbryt, Jolanta Pamula-Pilat, Katarzyna M. Lisowska, Ewa Grzybowska, Tymon Rubel, Agnieszka Dansonka-Mieszkowska, Bozena Konopka, Magdalena Kulesza, Martyna Lukasik, Jolanta Kupryjanczyk

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Oncotarget. 2015; 6:43897-43910. https://doi.org/10.18632/oncotarget.6016

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Abstract

Lukasz Michal Szafron1,*, Anna Balcerak2,*, Ewa Anna Grzybowska2, Barbara Pienkowska-Grela1, Agnieszka Podgorska1, Renata Zub2, Magdalena Olbryt3, Jolanta Pamula-Pilat3, Katarzyna M. Lisowska3, Ewa Grzybowska3, Tymon Rubel4, Agnieszka Dansonka-Mieszkowska1, Bozena Konopka1, Magdalena Kulesza1, Martyna Lukasik1, Jolanta Kupryjanczyk1,*

1Department of Pathology and Laboratory Diagnostics, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

2Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland

3Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Poland

4Institute of Radioelectronics and Multimedia Technology, Warsaw University of Technology, Warsaw, Poland

*These authors have contributed equally to this work

Correspondence to:

Lukasz Michal Szafron, e-mail: lukszafron@gmail.com

Keywords: ovarian cancer, prognostic factor, CRNDE, gene expression, TP53

Received: June 18, 2015     Accepted: October 06, 2015     Published: November 04, 2015

ABSTRACT

The CRNDE gene seems to play an oncogenic role in cancers, though its exact function remains unknown. Here, we tried to assess its usefulness as a molecular prognostic marker in ovarian cancer. Based on results of our microarray studies, CRNDE transcripts were further analyzed by Real-Time qPCR-based profiling of their expression. The qPCR study was conducted with the use of personally designed TaqMan assays on 135 frozen tissue sections of ovarian carcinomas from patients treated with platinum compounds and either cyclophosphamide (PC, N = 32) or taxanes (TP, N = 103). Elevated levels of two different CRNDE transcripts were a negative prognostic factor; they increased the risk of death and recurrence in the group of patients treated with TP, but not PC (DNA-damaging agents only). Higher associations were found for overexpression of the short CRNDE splice variant (FJ466686): HR 6.072, 95% CI 1.814–20.32, p = 0.003 (the risk of death); HR 15.53, 95% CI 3.812–63.28, p < 0.001 (the risk of recurrence). Additionally, accumulation of the TP53 protein correlated with decreased expression of both CRNDE transcripts in tumor cells. Our results depict CRNDE as a potential marker of poor prognosis in women with ovarian carcinomas, and suggest that its significance depends on the therapeutic regimen used.


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