title: Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients.
abstract: 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.
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Ning Qing
authors: NQ
authors: Liu
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.|Postgraduate School of Molecular Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Tommaso
authors: T
authors: De Marchi
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Annemieke
authors: A
authors: Timmermans
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Anita M A C
authors: AM
authors: Trapman-Jansen
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Renée
authors: R
authors: Foekens
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Maxime P
authors: MP
authors: Look
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Marcel
authors: M
authors: Smid
authors: Department of Pathology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Carolien H M
authors: CH
authors: van Deurzen
authors: Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Paul N
authors: PN
authors: Span
authors: Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Fred C G J
authors: FC
authors: Sweep
authors: Department of Pathology, Centre of Diagnostic Investigations, Copenhagen University Hospital, Copenhagen, Denmark.
authors: Julie Benedicte
authors: JB
authors: Brask
authors: Department of Pathology, Centre of Diagnostic Investigations, Copenhagen University Hospital, Copenhagen, Denmark.
authors: Vera
authors: V
authors: Timmermans-Wielenga
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: John A
authors: JA
authors: Foekens
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: John W M
authors: JW
authors: Martens
authors: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Arzu
authors: A
authors: Umar
mesh_terms: D000328:Adult; D000368:Aged; D002467:Cell Nucleus / Q000201:enzymology; D016208:Databases, Factual; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009703:Nucleoside-Phosphate Kinase / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000401:mortality* / Q000473:pathology / Q000628:therapy
chemical_list: C019979:cytidylate kinase; D009703:Nucleoside-Phosphate Kinase