title: Transcriptomic analyses identify association between mitotic kinases, PDZ-binding kinase and BUB1, and clinical outcome in breast cancer.
abstract: Protein kinases are important components in oncogenic transformation of breast cancer. Evaluation of upregulated genes that codify for protein kinases could be used as biomarkers to predict clinical outcome. Gene expression and functional analyses using public datasets were performed to identify differential gene expression and functions in basal-like tumors compared with normal breast tissue. Overall survival (OS) associated with upregulated genes was explored using the KM Plotter online tool. The prognostic influence of these genes in luminal tumors and systemically untreated patients was also assessed. Of the 426 transcripts identified in basal-like tumors, 11 genes that coded for components of protein kinases were upregulated with more than a fourfold change. Regulation of cell cycle was an enriched function containing 10 of these 11 identified genes. Among them, expression of four genes, BUB1β, CDC28, NIMA, and PDZ binding kinase, were all associated with improved OS when using at least one probe in the basal-like subtype. Two genes, BUB1β and PDZ binding kinase, showed consistent association with improved OS irrespective of the gene probe used for the analysis. No association was observed for these genes with relapse-free survival. In contrast, both BUB1β and PDZ binding kinase showed worse OS in luminal tumors and in a cohort of systemically untreated patients. BUB1β and PDZ binding kinase are associated with improved OS in basal-like tumors and worse OS in luminal and untreated patients. The association with a better outcome in basal-like tumors could be due to a more favorable response to chemotherapy.
authors.affiliation: Translational Research Unit, Albacete University Hospital, Calle Francisco Javier de Moya, 02006, Albacete, Spain. albertoo@sescam.jccm.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocaña
authors.affiliation: Translational Research Unit, Albacete University Hospital, Calle Francisco Javier de Moya, 02006, Albacete, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-Peña
authors.affiliation: Translational Research Unit, Albacete University Hospital, Calle Francisco Javier de Moya, 02006, Albacete, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Díez-González
authors.affiliation: Translational Research Unit, Albacete University Hospital, Calle Francisco Javier de Moya, 02006, Albacete, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Sánchez-Corrales
authors.affiliation: Department of Medical Oncology and Hematology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
authors.forename: Arnoud
authors.initials: A
authors.lastname: Templeton
authors.affiliation: Department of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Bostjan
authors.initials: B
authors.lastname: Seruga
authors.affiliation: Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada.
authors.forename: Eitan
authors.initials: E
authors.lastname: Amir
authors.affiliation: IBMCC, CSIC-University of Salamanca, Salamanca, Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D003198:Computer Simulation; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics*; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C409022:PDZ-binding kinase
keywords: BUB1; Breast cancer; Mitotic kinases; PDZ binding kinase