title: In silico analyses identify gene-sets, associated with clinical outcome in ovarian cancer: role of mitotic kinases.
abstract: BACKGROUND
  Accurate assessment of prognosis in early stage ovarian cancer is challenging resulting in suboptimal selection of patients for adjuvant therapy. The identification of predictive markers for cytotoxic chemotherapy is therefore highly desirable. Protein kinases are important components in oncogenic transformation and those relating to cell cycle and mitosis control may allow for identification of high-risk early stage ovarian tumors.
  
  
  METHODS
  Genes with differential expression in ovarian surface epithelia (OSE) and ovarian cancer epithelial cells (CEPIs) were identified from public datasets and analyzed with dChip software. Progression-free (PFS) and overall survival (OS) associated with these genes in stage I/II and late stage ovarian cancer was explored using the Kaplan Meier Plotter online tool.
  
  
  RESULTS
  Of 2925 transcripts associated with modified expression in CEPIs compared to OSE, 66 genes coded for upregulated protein kinases. Expression of 9 of these genes (CDC28, CHK1, NIMA, Aurora kinase A, Aurora kinase B, BUB1, BUB1βB, CDKN2A and TTK) was associated with worse PFS (HR:3.40, log rank p<0.001). The combined analyses of CHK1, CDKN2A, AURKA, AURKB, TTK and NEK2 showed the highest magnitude of association with PFS (HR:4.62, log rank p<0.001). Expression of AURKB predicted detrimental OS in stage I/II ovarian cancer better than all other combinations Conclusion: Genes linked to cell cycle control are associated with worse outcome in early stage ovarian cancer. Incorporation of these biomarkers in clinical studies may help in the identification of patients at high risk of relapse for whom optimizing adjuvant therapeutic strategies is needed.
authors.affiliation: Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ocaña
authors.affiliation: Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Pérez-Peña
authors.affiliation: Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Alcaraz-Sanabria
authors.affiliation: Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Sánchez-Corrales
authors.affiliation: Translational Research Unit, Albacete University Hospital, Albacete, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nieto-Jiménez
authors.affiliation: Department of Medical Oncology and Hematology, St Gallen, Switzerland.
authors.forename: Arnoud J
authors.initials: AJ
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: Cancer Research Center, CSIC-University of Salamanca, Spain.
authors.forename: Atanasio
authors.initials: A
authors.lastname: Pandiella
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
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism*; D000077216:Carcinoma, Ovarian Epithelial; D066264:Datasets as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D011494:Protein Kinases / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D011494:Protein Kinases
keywords: AURKB; cell cycle; mitotic kinases; ovarian cancer; protein kinases