Development of Autoantibody Signatures as Biomarkers for Early Detection of Colorectal Carcinoma

Abstract

Purpose: To select autoantibody signatures for early detection of colorectal cancer (CRC). Experimental Design: A phage cDNA expression library was constructed with fresh tumors from 30 CRC patients and biopanned by using serum pools of 20 CRC patients and 20 healthy controls. A classifier was discovered in the training set of 30 CRC patients at stages I and II and 30 matched healthy controls and then blindly validated in an independent set of 60 CRC patients, 60 healthy controls, 52 polyps patients, and 30 autoimmune diseases patients. Expression of proteins was examined by using immunohistochemistry.Results: Five-phage peptide clones showing higher discriminatory power than others in training set were selected for validation. The five-phage peptide classifier was able to discriminate between early CRC patients and healthy controls, with sensitivities of 90.0% to 92.7% and specificities of 91.7% to 93.3%. In those with serum carcinoembryonic antigen less than 5 ng/mL, the classifier was efficient in discriminating CRC from healthy controls, with an area under the curve of 0.975. The classifier was able to discriminate all of the 9 patients with serrated adenoma from healthy controls. Thirteen (43.3%) of the patients with autoimmune diseases were misclassified. Of the five phage peptides, one encoded a peptide identical to immunoglobulin G (IgG) heavy-chain constant region. IgG immunostaining was stronger in mesenchymal cells than in cancer cells in the tumors and was apparent in serrated adenoma.Conclusions: The five-phage peptide classifier stands out as promising early diagnostic biomarkers for CRC, but it is unsuitable for discriminating CRC from autoimmune diseases. Truncated IgGs generated from the tumors might be novel CRC-associated antigens. Clin Cancer Res; 17(17); 5715-24. Ó2011 AACR.

Autoantibody Signatures Combined with Epstein–Barr Virus Capsid Antigen-IgA as a Biomarker Panel for the Detection of Nasopharyngeal Carcinoma

“…In patients with earlystage NPC, use of the autoantibody panel provided a better diagnostic efficacy (Table 3). This indicates that the autoantibody panel may be a promising marker for the early detection of NPC and that the induction of autoantibodies occurs early in the process of carcinogenesis, which is consistent with previous studies (9)(10)(11)(12)(13)(14)(15)(16)(17). Analysis of VCA-IgA presented here is also shown to be a useful diagnostic biomarker of NPC, which is in agreement with a study by Ai and colleagues (21), but the high false-negative rates will prevent the timely diagnosis of NPC patients in endemic areas, particularly the symptomless, early-stage patients.…”

“…Autoantibodies have attracted more attention as possible biomarkers in recent years. A large number of studies describe the presence of autoantibodies to tumorassociated antigens (TAA) in serum samples from patients with a variety of cancers (9)(10)(11)(12)(13)(14)(15). Interestingly, autoantibodies seem to appear months to years before the clinical diagnosis of a tumor, which makes measurement of autoantibodies suitable for earlystage cancer diagnosis (9,14,15).…”

High level of WAVE1 expression is associated with tumor aggressiveness and unfavorable prognosis of epithelial ovarian cancer

“…To the best of our knowledge, the immune system of patients with cancers actively monitors and elicits T-cell and autoantibodies against tumor-associated antigens [26,27]. Some studies have demonstrated the appearance of serum autoantibodies as biomarkers for early diagnosis of human cancers [28][29][30]. Together, these clinical analyses clearly suggested that WAVE1 protein expression is a novel independent prognostic factor and biomarker of unfavorable outcomes from EOC.…”

Tumormarker zur Früherkennung – sinnvoll oder sinnlos?

“…Dieser Nachteil lässt einen Screeningeinsatz als noch nicht erfolgversprechend erscheinen. Er konnte jedoch in einigen Arbeiten durch die Bildung von Kombinations-Panels teilweise wettgemacht werden [21][22][23].…”