Tumor Biology

, Volume 36, Issue 4, pp 2473–2480 | Cite as

Diagnostic significance of alternative splice variants of REST and DOPEY1 in the peripheral blood of patients with breast cancer

  • Ave Kris Lend
  • Anna Kazantseva
  • Anri Kivil
  • Vahur Valvere
  • Kaia Palm
Research Article

Abstract

Changes in alternative splicing have been linked to cancer development. We hypothesized that changes occurring in tumor tissue can also be detected in the peripheral blood of cancer patients leading to discovery of blood biomarkers of breast cancer. Alternative splicing profiles of 94 genes were examined in cancerous breast tissue. Discriminating splice variants were analyzed in the peripheral blood of early stage (BCI/II) (stage I–II; n = 26), neoadjuvant receiving locally advanced breast cancer patients (LABC) (stage IIb–IIIa, b; n = 10) and healthy volunteers (n = 26) using qRT-PCR analysis. Changes in marker expression during neoadjuvant therapy were analyzed at 15 timepoints. High expression of REST-N50, the alternatively spliced variant of REST, was detected in the blood of LABC patients but not in BCI/II and healthy controls (p = 0.0032 and p = 0.0029, respectively). Expression levels of DOPEY1v2, the alternative splice variant of DOPEY1, in the blood could differentiate cancer from healthy controls (p = 0.024) and discriminate between patient groups (BCI/II vs LABC, p = 0.002). Positive response to neoadjuvant therapy of REST-N50-positive LABC patients correlated with a decrease in REST-N50 levels (p < 0.0001). Assessment of REST-N50 and DOPEY1v2 may prove useful in diagnostic blood tests of breast cancer. REST-N50 shows a high potential as a blood biomarker for evaluating the effectiveness of therapy in the neoadjuvant setting.

Keywords

Alternative splicing Locally advanced breast cancer Neoadjuvant therapy Blood REST DOPEY1 

Notes

Acknowledgments

This study was supported by Protobios’s grants from the Enterprise of Estonia and baseline financing from the Estonian Ministry of Education and Research. We are grateful to Dr. Jõeste and NEMC for the tissue samples. We thank K.J.M. Rand for the work with in silico database, primer design, and cloning; Dr. Pruunsild and Prof. Timmusk for the resources provided; and K. Taal and H. Verev for the technical help in sample handling.

Conflicts of interest

None.

Supplementary material

13277_2014_2860_MOESM1_ESM.pdf (108 kb)
ESM 1 (PDF 107 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ave Kris Lend
    • 1
    • 2
  • Anna Kazantseva
    • 1
  • Anri Kivil
    • 1
    • 3
  • Vahur Valvere
    • 2
    • 4
  • Kaia Palm
    • 1
    • 2
    • 3
  1. 1.Protobios LLCTallinnEstonia
  2. 2.Competence Center for Cancer ResearchTallinnEstonia
  3. 3.The Department of Gene TechnologyTallinn University of TechnologyTallinnEstonia
  4. 4.Clinic of Hematology and OncologyNorth Estonia Medical CenterTallinnEstonia

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