title: ATAD2 overexpression links to enrichment of B-MYB-translational signatures and development of aggressive endometrial carcinoma.
abstract: We have explored the potential for clinical implementation of ATAD2 as a biomarker for aggressive endometrial cancer by investigating to what extent immunohistochemical (IHC) staining for ATAD2 is feasible, reflects clinical phenotype and molecular subgroups of endometrial carcinomas. Increased expression of the ATAD2 gene has been implicated in cancer development and progression in a number of tissues, but few studies have investigated ATAD2 expression using IHC. Here we show that high ATAD2 protein expression is significantly associated with established clinical-pathological variables for aggressive endometrial cancer, also in the subset of estrogen receptor α (ERα) positive tumors. Protein and mRNA expression of ATAD2 were highly correlated (P < 0.001), suggesting that IHC staining may represent a more clinically applicable measure of ATAD2 level in routinely collected formalin fixed paraffin embedded specimens. Gene expression alterations in samples with high ATAD2 expression revealed upregulation of several cancer-related genes (B-MYB, CDCs, E2Fs) and gene sets that previously have been linked to aggressive disease and potential for new targeting therapies. Our results support that IHC staining for ATAD2 may be a clinically applicable biomarker reflecting clinical phenotype and targetable alterations in endometrial carcinomas to be further explored in controlled clinical trials.
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Camilla
authors: C
authors: Krakstad
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Ingvild L
authors: IL
authors: Tangen
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Erling A
authors: EA
authors: Hoivik
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Mari K
authors: MK
authors: Halle
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Anna
authors: A
authors: Berg
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Henrica M
authors: HM
authors: Werner
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Maria B
authors: MB
authors: Ræder
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.|Computational Biology Unit, University of Bergen, Bergen, Norway.
authors: Kanthida
authors: K
authors: Kusonmano
authors: Department of Internal Medicine and Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA.
authors: June X
authors: JX
authors: Zou
authors: Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors: Anne M
authors: AM
authors: Øyan
authors: Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors: Ingunn
authors: I
authors: Stefansson
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Jone
authors: J
authors: Trovik
authors: Centre for Cancer Biomarkers, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Microbiology, Haukeland University Hospital, Bergen, Norway.
authors: Karl-Henning
authors: KH
authors: Kalland
authors: Department of Internal Medicine and Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California, Davis, CA, USA.
authors: Hong-Wu
authors: HW
authors: Chen
authors: Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
authors: Helga B
authors: HB
authors: Salvesen
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D015534:Trans-Activators; D000251:Adenosine Triphosphatases; C544857:ATAD2 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: ATAD2; biomarker; endometrial cancer; molecular profiling