title: Verification of endometrial tissue biomarkers previously discovered using mass spectrometry-based proteomics by means of immunohistochemistry in a tissue microarray format.
abstract: Verification of candidate protein biomarkers is a necessary step in moving from the initial discovery to application. Here, we report results of a verification exercise involving six candidate endometrial cancer biomarkers previously discovered using mass-tagging and multidimensional liquid chromatography/tandem mass spectrometry (DeSouza L., et al. J. Proteome Res. 2005, 4, 377-386) on a cohort of 148 patient samples by means of immunohistochemistry on a tissue microarray format. A panel of the three best-performing biomarkers, chaperonin 10, pyruvate kinase M2, and alpha-1-antitrypsin, achieved a sensitivity of 0.85, specificity of 0.93, predictive value of 0.90, and positive predictive value of 0.88 in discriminating malignant from benign endometrium. The ruggedness of this panel of biomarkers was verified in a 2/3-training-set-1/3-test-set cross-validation analysis by randomly splitting the cohort in 10 ways. The roles of chaperonin 10 and pyruvate kinase M2 in tumorigenesis confirm them as credible cancer biomarkers.
authors.affiliation: Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: Dubé
authors.forename: Jörg
authors.initials: J
authors.lastname: Grigull
authors.forename: Leroi V
authors.initials: LV
authors.lastname: DeSouza
authors.forename: Shaun
authors.initials: S
authors.lastname: Ghanny
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Colgan
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: K W Michael
authors.initials: KW
authors.lastname: Siu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis* / Q000592:standards*; D002853:Chromatography, Liquid; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000473:pathology; D004717:Endometrium / Q000737:chemistry / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D013058:Mass Spectrometry; D040901:Proteomics / Q000379:methods; D046888:Tissue Array Analysis / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor