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. 2015 Oct 13;10(10):e0139965.
doi: 10.1371/journal.pone.0139965. eCollection 2015.

The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer

Laxmi Silwal-Pandit  1 , Hege Russnes  2 , Elin Borgen  3 , Veronica Skarpeteig  4 , Hans Kristian Moen Vollan  5 , Ellen Schlichting  6 , Rolf Kåresen  7 , Bjørn Naume  8 , Anne-Lise Børresen-Dale  1 , Marianne Farnebo  9 , Anita Langerød  4
Affiliations

The Sub-Cellular Localization of WRAP53 Has Prognostic Impact in Breast Cancer

Laxmi Silwal-Pandit et al. PLoS One. .

Abstract

WRAP53 protein controls intracellular trafficking of DNA repair proteins, the telomerase enzyme, and splicing factors. Functional loss of the protein has been linked to carcinogenesis, premature aging and neurodegeneration. The aim of this study was to investigate the prognostic significance of WRAP53 protein expression in breast cancer. A tissue microarray was constructed from primary breast tumors and immunostained by a polyclonal WRAP53 antibody to assess the protein expression pattern. Two different patient cohorts with long term follow-up were studied; a test- and a validation set of 154 and 668 breast tumor samples respectively. Breast cancer patients with tumor cells lacking the expression of WRAP53 in the nucleus had a significantly poorer outcome compared to patients with tumor cells expressing this protein in the nuclei (HR = 1.95, 95%CI = 1.09-3.51, p = 0.025). Nuclear localization of WRAP53 was further shown to be an independent marker of prognosis in multivariate analysis (HR = 2.57, 95%CI = 1.27-5.19, p = 0.008), and also significantly associated with better outcome in patients with TP53 mutation. Here we show that the sub-cellular localization of the WRAP53 protein has a significant impact on breast cancer survival, and thus has a potential as a clinical marker in diagnostics and treatment.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Immunohistochemical staining patterns of WRAP53 in breast cancer.
A. and B. Positive nucleus/positive cytoplasma, C. and D. positive nucleus/negative cytoplasma (with normal mammary epithelial cells), E. positive nucleus/negative cytoplasm (invasive lobular carcinoma), and F. negative nucleus/negative cytoplasm.
Fig 2
Fig 2
Kaplan-Meier curves showing Breast Cancer Specific Survival (BCSS) of WRAP53 IHC staining of nucleus and cytoplasm A. in the test set and B. in the validation set. C. BCSS of WRAP53 nuclear IHC staining in validation set categorized based on fraction of stained cells. 0: no tumor cells with distinct staining of the nucleus, 1: <5% of the cells stained, 2: 5–50% of the cells stained, 3: 50–75% of the cells stained, and 4: >75% of the cells stained. Numbers at risk are listed below each chart.
Fig 3
Fig 3
Kaplan-Meier curves showing Breast Cancer Specific Survival (BCSS) of WRAP53 IHC staining of nucleus and cytoplasm in combination, A. in the test set and B. in the validation set. Numbers at risk are listed below each chart.
See this image and copyright information in PMC

References

    1. Mahmoudi S, Henriksson S, Corcoran M, Méndez-Vidal C, Wiman KG, Farnebo M. Wrap53, a natural p53 antisense transcript required for p53 induction upon DNA damage. Mol. Cell. 2009;33:462–71. 10.1016/j.molcel.2009.01.028 - DOI - PubMed
    1. Venteicher AS, Abreu EB, Meng Z, McCann KE, Terns RM, Veenstra TD, et al. A human telomerase holoenzyme protein required for Cajal body localization and telomere synthesis. Science. 2009;323:644–8. 10.1126/science.1165357 - DOI - PMC - PubMed
    1. Tycowski KT, Shu M-D, Kukoyi A, Steitz JA. A conserved WD40 protein binds the Cajal body localization signal of scaRNP particles. Mol. Cell. 2009;34:47–57. 10.1016/j.molcel.2009.02.020 - DOI - PMC - PubMed
    1. Mahmoudi S, Henriksson S, Weibrecht I, Smith S, Söderberg O, Strömblad S, et al. WRAP53 is essential for Cajal body formation and for targeting the survival of motor neuron complex to Cajal bodies. PLoS Biol. 2010;8:e1000521 10.1371/journal.pbio.1000521 - DOI - PMC - PubMed
    1. Henriksson S, Rassoolzadeh H, Hedstrom E, Coucoravas C, Julner A, Goldstein M, et al. The scaffold protein WRAP53B orchestrates the ubiquitin response critical for DNA double-strand break repair. 2014;2726–38. - PMC - PubMed

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