Oncotarget

Research Papers:

CCAT2, a novel long non-coding RNA in breast cancer: expression study and clinical correlations

Roxana S Redis, Anieta M Siewerts, Maxime P Look, Oana Tudoran, Cristina Ivan, Riccardo Spizzo, Xinna Zhang, Vanja de Weerd, Masayoshi Shimizu, Hui Ling, Rares Buiga, Victor Pop, Alexandru Irimie, Riccardo Fodde, Isabella Bedrosian, John WM Martens, John A Foekens, Ioana Berindan-Neagoe and George A Calin _

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Oncotarget. 2013; 4:1748-1762. https://doi.org/10.18632/oncotarget.1292

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Abstract

Roxana S Redis1,3,*, Anieta M Sieuwerts2,*, Maxime P Look2, Oana Tudoran4, Cristina Ivan6 , Riccardo Spizzo5, Xinna Zhang6, Vanja de Weerd2, Masayoshi Shimizu1, Hui Ling1, Rares Buiga10, Victor Pop3, Alexandru Irimie11, Riccardo Fodde7, Isabella Bedrosian8, John WM Martens2, John A Foekens2, Ioana Berindan-Neagoe4,9, George A Calin1,7

1 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

2 Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical, Rotterdam, The Netherlands

3 Department of Molecular Science, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.

4 Department of Functional Genomics, The Oncology Institute, Cluj-Napoca, Romania.

5 Division of Experimental Oncology, CRO, National Cancer Institute, Aviano, Italy.

6 Center for RNA Interference and Non-coding RNAs The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

7 Department of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, Rotterdam, The Netherlands.

8 Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

9 Research Center for Functional Genomics, Biomedicine and Translational Medicine, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.

10 Department of Pathology, The Oncology Institute, Cluj-Napoca, Romania

11 Department of Surgical and Gynecology Oncology, University of Medicine and Pharmacy Iuliu Hatieganu, Cluj-Napoca, Romania.

* These authors contributed equally to this work

Correspondence:

George A. Calin, email:

Ioana Berindan-Neagoe, email:

Keywords: non coding RNA, CCAT2, breast cancer, prognosis, real-time PCR.

Received: August 15, 2013 Accepted: September 16, 2013 Published: September 18, 2013

Abstract

The clinical outcome of BC patients receiving the same treatment is known to vary considerably and thus, there is a compelling need to identify novel biomarkers that can select the patients that would benefit most from a given therapy and can predict the clinical outcome. The aim of this study was to determine the prognostic value of CCAT2, a novel long ncRNA recently characterized by our group and overlapping SNP rs6983267, in BC patients. We first evaluated by RT-qPCR and ISH the expression of CCAT2 in normal breast tissue and BC tissue and further analyzed CCAT2 expression in an independent set of 997 primary BC with regard to clinical, histological, pathological and other biological factors. Also, we explored the possibility of CCAT2 adding to the prognostic value of multivariate models that already included the traditional prognostic factors. Finally, we identified in in vitro models the impact of CCAT2 expression and SNP rs6983267 genotype on cell migration and chemoresistance. Our results revealed that although overexpressed in BCs in two out of three sets of patients, and having the highest expression in lymph node negative (LNN) disease, CCAT2 expression levels are informative solely for a subgroup of BC patients, namely for patients with LNP disease that have received adjuvant CMF chemotherapy. For this subgroup high levels of CCAT2 suggest the patients will not benefit from CMF containing adjuvant chemotherapy (shorter MFS and OS). Additionally, we found that CCAT2 upregulates cell migration and downregulates chemosensitivity to 5’FU in a rs6983267-independent manner.


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