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01.04.2015 | Research Article | Ausgabe 4/2015

Tumor Biology 4/2015

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

Zeitschrift:
Tumor Biology > Ausgabe 4/2015
Autoren:
Ave Kris Lend, Anna Kazantseva, Anri Kivil, Vahur Valvere, Kaia Palm
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1007/​s13277-014-2860-6) contains supplementary material, which is available to authorized users.
Ave Kris Lend and Anna Kazantseva contributed equally to this work.

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.

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Zusatzmaterial
ESM 1 (PDF 107 kb)
13277_2014_2860_MOESM1_ESM.pdf
Literatur
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