Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients

• Published in: Scientific reports Vol. 6; no. 1; p. 32027
• Main Authors: Liu, Ning Qing, De Marchi, Tommaso, Timmermans, Annemieke, Trapman-Jansen, Anita M. A. C., Foekens, Renée, Look, Maxime P., Smid, Marcel, van Deurzen, Carolien H. M., Span, Paul N., Sweep, Fred C. G. J., Brask, Julie Benedicte, Timmermans-Wielenga, Vera, Foekens, John A., Martens, John W. M., Umar, Arzu
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 25.08.2016; Nature Publishing Group
• Subjects: 14/105; 45; 45/61; 692/4028/67/1347; 692/53/2422; 82; 82/58; Adult; Aged; Breast cancer; Cell cycle; Cell Nucleus - enzymology; Correlation analysis; Databases, Factual; Extracellular matrix; Extracellular Matrix - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene set enrichment analysis; Humanities and Social Sciences; Humans; Immunohistochemistry; Kinases; Mass spectroscopy; Medical prognosis; Metastases; Middle Aged; multidisciplinary; Nucleoside-Phosphate Kinase - genetics; Nucleoside-Phosphate Kinase - metabolism; Paraffin; Prognosis; Science; Tissue Array Analysis; Triple Negative Breast Neoplasms - enzymology; Triple Negative Breast Neoplasms - mortality; Triple Negative Breast Neoplasms - pathology; Triple Negative Breast Neoplasms - therapy
• DOI: 10.1038/srep32027
• ISSN: 2045-2322

We have previously identified UMP-CMP kinase (CMPK1) as a prognostic marker for triple negative breast cancer (TNBC) by mass spectrometry (MS). In this study we evaluated CMPK1 association to prognosis in an independent set of samples by immunohistochemistry (IHC) and assessed biological pathways associated to its expression through gene set enrichment analysis (GSEA). A total of 461 TNBC paraffin-embedded tissues were collected from different academic hospitals in Europe, incorporated into tissue micro-arrays (TMA), and stained for CMPK1 expression. We also collected gene expression data of 60 samples, which were also present in the TMA, for GSEA correlation analysis. CMPK1 IHC staining showed both cytoplasmic and nuclear components. While cytoplasmic CMPK1 did not show any association to metastasis free survival (MFS), nuclear CMPK1 was associated to poor prognosis independently from other prognostic factors in stratified Cox regression analyses. GSEA correlation analysis of the nuclear CMPK1-stratified gene expression dataset showed a significant enrichment of extracellular matrix (ECM; positive correlation) and cell cycle (negative correlation) associated genes. We have shown here that nuclear CMPK1 is indicative of poor prognosis in TNBCs and that its expression may be related to dysregulation of ECM and cell cycle molecules.