Identifying novel autoantibody signatures in ovarian cancer using high-density protein microarrays
ABSTRACT Objectives: To identify autoantibody signatures in ovarian cancer using protein microarray technology. Design and methods: Protein microarrays were screened using non-malignant peritoneal fluid (n=30) and ascites fluid pooled from ovarian cancer patients (n=30). Results: Fifteen potential tumour-associated antigens were discovered. AASDHPPT showed the strongest signal-to-noise ratio. Conclusions: Protein microarrays are suitable for autoantibody discovery in ovarian cancer but the signatures are of low frequency.
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ABSTRACT: Sera from patients with ovarian cancer contain autoantibodies (AAb) to tumor-derived proteins that are potential biomarkers for early detection. To detect AAb, we probed high-density programmable protein microarrays (NAPPA) expressing 5,177 candidate tumor antigens with sera from patients with serous ovarian cancer (n=34 cases/30 controls) and measured bound IgG. Of these, 741 antigens were selected and probed with an independent set of ovarian cancer sera (n=58 cases/60 controls). Twelve potential autoantigens were identified with sensitivities ranging from 13-22% at >93% specificity. These were retested using a Luminex bead arrays using 60 cases and 60 controls, with sensitivities ranging from 0-31.7% at 95% specificity. Three AAb (p53, PTPRA, and PTGFR) had area under the curve (AUC) levels>60% (p<0.01), with the partial AUC (SPAUC) over 5 times greater than for a non-discriminating test (p<0.01). Using a panel of the top three AAb (p53, PTPRA, and PTGFR), if at least two AAb were positive, the sensitivity was 23.3% at 98.3% specificity. AAb to at least one of these top three antigens were also detected in 7/20 sera (35%) of patients with low CA125 levels and 0/15 controls. AAb to p53, PTPRA, and PTGFR are potential biomarkers for the early detection of ovarian cancer.Journal of Proteome Research 11/2014; 14(1). DOI:10.1021/pr500908n · 5.00 Impact Factor
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ABSTRACT: Proteomic analysis of cancer tissues and cells provides valuable information to identify promising targets for cancer diagnosis, prognosis and therapy. Novel strategies have emerged to optimize the workflow of tissue procurement, and tissue and cell selection, and to improve protocols for the extraction of protein from fresh, frozen and paraffin-embedded tissue. Moreover, in the context of advanced approaches to proteomics, mass spectrometry and array-based technologies strongly contribute to protein profiling of cancer tissues and cells.The focus of this review is the methods by which all the steps of a proteomic investigation on human-cancer tissue (from choice of the experimental model to validation of candidate biomarkers) should be performed, paying particular attention to recently developed strategies. The review also presents an overview of the most recent high-throughput proteomic studies in cancer research.TrAC Trends in Analytical Chemistry 02/2011; 30(2):346-359. DOI:10.1016/j.trac.2010.10.016 · 6.61 Impact Factor
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ABSTRACT: Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in both men and women, posing a serious demographic and economic burden worldwide. In the United Kingdom, CRC affects 1 in every 20 people and it is often detected once well established and after it has spread beyond the bowel (Stage IIA-C and Stage IIIA-C). A diagnosis at such advanced stages is associated with poor treatment response and survival. However, studies have identified two sub-groups of post-treatment CRC patients-those with good outcome (reactive disease) and those with poor outcome (non-reactive disease). We aim to review the state-of-the-art for CRC with respect to the expression of cancer-testis antigens (CTAs) and their identification, evaluation and correlation with disease progression, treatment response and survival. We will also discuss the relationship between CTA expression and regulatory T-cell (Treg) activity to tumorigenesis and tumor immune evasion in CRC and how this could account for the clinical presentation of CRC. Understanding the molecular basis of reactive CRC may help us identify more potent novel immunotherapeutic targets to aid the effective treatment of this disease. In this review, based on our presentation at the 2012 International Society for the Cell and Gene Therapy of Cancer annual meeting, we will summarize some of the most current advances in CTA and CRC research and their influence on the development of novel immunotherapeutic approaches for this common and at times difficult to treat disease.Cancer Gene Therapy advance online publication, 15 March 2013; doi:10.1038/cgt.2013.5.Cancer gene therapy 03/2013; DOI:10.1038/cgt.2013.5 · 2.55 Impact Factor