CCAT2, a novel long non-coding RNA in breast cancer

Expression study and clinical correlations

Roxana S. Redis, Anieta M. Sieuwerts, 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 W M Martens, John A. Foekens, Ioana Berindan-Neagoe, George A. Calin

Research output: Contribution to journalArticle

128 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1748-1762
Number of pages15
JournalOncotarget
Volume4
Issue number10
Publication statusPublished - Oct 2013

Fingerprint

Long Noncoding RNA
Breast Neoplasms
Adjuvant Chemotherapy
Cell Movement
Single Nucleotide Polymorphism
Biological Factors
Clinical Studies
Fluorouracil
Breast
Up-Regulation
Down-Regulation
Biomarkers
Lymph Nodes
Genotype
Therapeutics

Keywords

  • Breast cancer
  • CCAT2
  • Non coding RNA
  • Prognosis
  • Real-time PCR

ASJC Scopus subject areas

  • Oncology

Cite this

Redis, R. S., Sieuwerts, A. M., Look, M. P., Tudoran, O., Ivan, C., Spizzo, R., ... Calin, G. A. (2013). CCAT2, a novel long non-coding RNA in breast cancer: Expression study and clinical correlations. Oncotarget, 4(10), 1748-1762.

CCAT2, a novel long non-coding RNA in breast cancer : Expression study and clinical correlations. / Redis, Roxana S.; Sieuwerts, Anieta M.; Look, Maxime P.; Tudoran, Oana; Ivan, Cristina; Spizzo, Riccardo; Zhang, Xinna; de Weerd, Vanja; Shimizu, Masayoshi; Ling, Hui; Buiga, Rares; Pop, Victor; Irimie, Alexandru; Fodde, Riccardo; Bedrosian, Isabella; Martens, John W M; Foekens, John A.; Berindan-Neagoe, Ioana; Calin, George A.

In: Oncotarget, Vol. 4, No. 10, 10.2013, p. 1748-1762.

Research output: Contribution to journalArticle

Redis, RS, Sieuwerts, AM, Look, MP, Tudoran, O, Ivan, C, Spizzo, R, Zhang, X, de Weerd, V, Shimizu, M, Ling, H, Buiga, R, Pop, V, Irimie, A, Fodde, R, Bedrosian, I, Martens, JWM, Foekens, JA, Berindan-Neagoe, I & Calin, GA 2013, 'CCAT2, a novel long non-coding RNA in breast cancer: Expression study and clinical correlations', Oncotarget, vol. 4, no. 10, pp. 1748-1762.
Redis RS, Sieuwerts AM, Look MP, Tudoran O, Ivan C, Spizzo R et al. CCAT2, a novel long non-coding RNA in breast cancer: Expression study and clinical correlations. Oncotarget. 2013 Oct;4(10):1748-1762.
Redis, Roxana S. ; Sieuwerts, Anieta M. ; Look, Maxime P. ; Tudoran, Oana ; Ivan, Cristina ; Spizzo, Riccardo ; Zhang, Xinna ; de Weerd, Vanja ; Shimizu, Masayoshi ; Ling, Hui ; Buiga, Rares ; Pop, Victor ; Irimie, Alexandru ; Fodde, Riccardo ; Bedrosian, Isabella ; Martens, John W M ; Foekens, John A. ; Berindan-Neagoe, Ioana ; Calin, George A. / CCAT2, a novel long non-coding RNA in breast cancer : Expression study and clinical correlations. In: Oncotarget. 2013 ; Vol. 4, No. 10. pp. 1748-1762.
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