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

• Published in: PloS one Vol. 10; no. 10; p. e0139965
• Main Authors: Silwal-Pandit, Laxmi, Russnes, Hege, Borgen, Elin, Skarpeteig, Veronica, Moen Vollan, Hans Kristian, Schlichting, Ellen, Kåresen, Rolf, Naume, Bjørn, Børresen-Dale, Anne-Lise, Farnebo, Marianne, Langerød, Anita
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13-10-2015; Public Library of Science (PLoS)
• Subjects: Aging; Analysis; Apoptosis; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer patients; Carcinogenesis; Carcinogens; Cell Nucleus - metabolism; Clinical medicine; Deoxyribonucleic acid; DNA; DNA microarrays; DNA repair; Enzymes; Female; Gene expression; Genomes; Hospitals; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Localization; Medical prognosis; Medical research; Medicin och hälsovetenskap; Medicine; Multivariate Analysis; Mutation; Neurodegeneration; Nuclei (cytology); Oncology; Ovarian cancer; p53 Protein; Pathology; Patients; Prognosis; Proportional Hazards Models; Protein Transport; Proteins; Radiation therapy; Splicing factors; Subcellular Fractions; Surgery; Telomerase; Telomerase - metabolism; Tumor cells; Tumor proteins; Tumors; Norway
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139965

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.