Adeola Henry A, Smith Muneerah, Kaestner Lisa, Blackburn Jonathan M, Zerbini Luiz F
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.
Oncotarget. 2016 Mar 22;7(12):13945-64. doi: 10.18632/oncotarget.7359.
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.
非洲对用于前列腺癌(PCa)早期诊断和治疗监测的高通量诊断工具的需求日益增长。癌症睾丸抗原(CTA)在非洲裔男性PCa中的作用研究较少。因此,我们旨在使用抗原微阵列平台,对来自南非PCa、良性前列腺增生(BPH)和疾病对照组(DC)队列的血液样本(N = 67)中的123种肿瘤相关抗原(TAA)的作用进行阐明。对自身抗体信号强度进行线性(超过临界值倍数)和差异表达定量分析。鉴定并分析候选PCa抗原生物标志物的分子特征,以了解种族差异。得出潜在的癌症诊断和免疫治疗推断。我们共鉴定出41种PCa潜在诊断/治疗抗原生物标志物。通过线性定量分析,发现与BPH相比,PCa血清中有四种抗原GAGE1、ROPN1、SPANXA1和PRKCZ的自身抗体滴度更高,其中MAGEB1和PRKCZ在BPH中高表达。此外,发现p53 S15A和p53 S46A在疾病对照组中高表达。差异表达的统计分析显示,与BPH和DC相比,PCa样本中有24种抗原上调,11种抗原下调(FDR = 0.01)。FGFR2、COL6A1和CALM1是使用尿鸟枪法蛋白质组学分析PCa的可验证生物标志物。对已鉴定生物标志物的功能通路注释显示,在基因组和蛋白质组水平上均有相似的富集,并且观察到种族差异。癌症抗原阵列在潜在诊断和免疫治疗抗原生物标志物发现中越来越有用。