title: Proteomic Profiling of Serial Prediagnostic Serum Samples for Early Detection of Colon Cancer in the U.S. Military.
abstract: Background:Serum proteomic biomarkers offer a promising approach for early detection of cancer. In this study, we aimed to identify proteomic profiles that could distinguish colon cancer cases from controls using serial prediagnostic serum samples.Methods:This was a nested case-control study of active duty military members. Cases consisted of 264 patients diagnosed with colon cancer between 2001 and 2009. Controls were matched to cases on age, gender, race, serum sample count, and collection date. We identified peaks that discriminated cases from controls using random forest data analysis with a 2/3 training and 1/3 validation dataset. We then included epidemiologic data to see whether further improvement of model performance was obtainable. Proteins that corresponded to discriminatory peaks were identified.Results:Peaks withm/zvalues of 3,119.32, 2,886.67, 2,939.23, and 5,078.81 were found to discriminate cases from controls with a sensitivity of 69% and a specificity of 67% in the year before diagnosis. When smoking status was included, sensitivity increased to 76% while histories of other cancer and tonsillectomy raised specificity to 76%. Peaks at 2,886.67 and 3,119.32m/zwere identified as histone acetyltransferases while 2,939.24m/zwas a transporting ATPase subunit.Conclusions:Proteomic profiles in the year before cancer diagnosis have the potential to discriminate colon cancer patients from controls, and the addition of epidemiologic information may increase the sensitivity and specificity of discrimination.Impact:Our findings indicate the potential value of using serum prediagnostic proteomic biomarkers in combination with epidemiologic data for early detection of colon cancer.Cancer Epidemiol Biomarkers Prev; 26(5); 711-8. ©2016 AACR.
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.|John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Shao
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC Proteomics Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Neely
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Tzu-Cheg
authors.initials: TC
authors.lastname: Kao
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Janet
authors.initials: J
authors.lastname: Eckhaus
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland.
authors.forename: Jolie
authors.initials: J
authors.lastname: Bourgeois
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC Proteomics Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Brooks
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC Proteomics Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Jones
authors.affiliation: Department of Cell and Molecular Pharmacology and Experimental Therapeutics and MUSC Proteomics Center, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Drake
authors.affiliation: Division of Epidemiology and Biostatistics, Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Kangmin.zhu@usuhs.edu.|John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland.
authors.forename: Kangmin
authors.initials: K
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D055088:Early Detection of Cancer / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D040901:Proteomics / Q000379:methods; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor