title: Novel potential serological prostate cancer biomarkers using CT100+ cancer antigen microarray platform in a multi-cultural South African cohort.
abstract: There is a growing need for high throughput diagnostic tools for early diagnosis and treatment monitoring of prostate cancer (PCa) in Africa. The role of cancer-testis antigens (CTAs) in PCa in men of African descent is poorly researched. Hence, we aimed to elucidate the role of 123 Tumour Associated Antigens (TAAs) using antigen microarray platform in blood samples (N = 67) from a South African PCa, Benign prostatic hyperplasia (BPH) and disease control (DC) cohort. Linear (fold-over-cutoff) and differential expression quantitation of autoantibody signal intensities were performed. Molecular signatures of candidate PCa antigen biomarkers were identified and analyzed for ethnic group variation. Potential cancer diagnostic and immunotherapeutic inferences were drawn. We identified a total of 41 potential diagnostic/therapeutic antigen biomarkers for PCa. By linear quantitation, four antigens, GAGE1, ROPN1, SPANXA1 and PRKCZ were found to have higher autoantibody titres in PCa serum as compared with BPH where MAGEB1 and PRKCZ were highly expressed. Also, p53 S15A and p53 S46A were found highly expressed in the disease control group. Statistical analysis by differential expression revealed twenty-four antigens as upregulated in PCa samples, while 11 were downregulated in comparison to BPH and DC (FDR = 0.01). FGFR2, COL6A1and CALM1 were verifiable biomarkers of PCa analysis using urinary shotgun proteomics. Functional pathway annotation of identified biomarkers revealed similar enrichment both at genomic and proteomic level and ethnic variations were observed. Cancer antigen arrays are emerging useful in potential diagnostic and immunotherapeutic antigen biomarker discovery.
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.|Faculty of Health Sciences, Division of Medical Biochemistry, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Henry A
authors.initials: HA
authors.lastname: Adeola
authors.affiliation: Faculty of Health Sciences, Division of Medical Biochemistry, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Muneerah
authors.initials: M
authors.lastname: Smith
authors.affiliation: Urology Department, Grootes Schuur Hospital, Cape Town, South Africa.
authors.forename: Lisa
authors.initials: L
authors.lastname: Kaestner
authors.affiliation: Faculty of Health Sciences, Division of Medical Biochemistry, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Blackburn
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, Cape Town, South Africa.|Faculty of Health Sciences, Division of Medical Biochemistry, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Zerbini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D055088:Early Detection of Cancer; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D011467:Prostate / Q000378:metabolism*; D011470:Prostatic Hyperplasia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011471:Prostatic Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D040081:Protein Array Analysis; D040901:Proteomics; D013019:South Africa / Q000453:epidemiology
chemical_list: D000951:Antigens, Neoplasm; D001323:Autoantibodies; D014408:Biomarkers, Tumor
keywords: biomarkers; cancer-testis antigen; prostate cancer; protein microarray; serum