Multiple serological biomarkers for colorectal cancer detection

Abstract

The aim of this study was to initiate a survey of human autoantibody responses to a panel of select colorectal tumorassociated antigens identified by previous serological analysis of a cDNA expression library and to subsequently identify multiple serological biomarkers for the detection of colorectal cancer. For screening of autoantibodies against colorectal tumor-associated antigens, sera from 94 colorectal cancer patients and 54 normal controls were analyzed by enzyme-linked immunosorbent assay using recombinant rCCCAP, rHDAC5, rP53, rNMDAR and rNY-CO-16 proteins as coating antigens. Seropositivity among colorectal cancer patients to the 5 individual coating antigens varied from 18.1% to 35.1%. Seropositivity to any of the 5 coating antigens was 58.5% and combining this analysis with evaluation of serum carcinoembryonic antigen (!5 ng/ml) significantly increased the seropositivity to 77.6%. Seropositivity of early-stage (Dukes' Stages A and B) colorectal cancer patients to CEA was 21.9%, and seropositivity to any of the 5 colorectal cancer-associated antigens was 53.7%, and the combination of these 2 measurements resulted in a higher diagnostic capacity (65.9%) than either marker alone. In conclusion, these results collectively indicated that combined detection of serum autoantibody profiles against our panel of colorectal tumor-associated antigens and the analysis of carcinoembryonic antigen provides a promising diagnostic biomarker for colorectal cancer, particularly among early-stage patients.

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

“…In the subjects with CEA level below 5 ng/mL, the classifier had a strong power in discriminating the CRC patients and the healthy controls, with an AUC of 0.975, indicating that the classifier might be able to fill in gaps of CEA in diagnosing early CRC. The classifier also has a higher validity than the reported arrays of some known CRC-associated antigens for the detection of CRC (21)(22)(23). Furthermore, OR for cases with the classification score more than 0.50 being associated with CRC was 99.0, which was much higher than an OR of 7.6 for G-FOBT and an OR of 18.7 for serum miR-92, the two methods recently reported for the early detection of CRC (28,29).…”

“…Profiling of circulating autoantibodies is therefore very attractive in diagnosing cancers at early stage. With the use of SEREX, protein array, and ELISA, autoantibodies to TAAs have been found in sera of the patients with CRC (14,(21)(22)(23). Although a panel of phage peptides developed by SEREX has high sensitivity and specificity in discriminating colon cancer patients with healthy controls, TAAs have not been fully identified (14).…”

“…Although a panel of phage peptides developed by SEREX has high sensitivity and specificity in discriminating colon cancer patients with healthy controls, TAAs have not been fully identified (14). Serum autoantibodies to some known TAAs have been documented to have relative low validity in discriminating CRC patients from healthy controls (22,23). Furthermore, the specificity of circulating autoantibodies for the detection of CRC has not been evaluated by using sera of the patients with precancerous polyps and those with autoimmune diseases.…”

Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

“…Autoantibodies can be produced in response to mutated, over- or aberrantly expressed TAAs and may provide an in vivo amplification in patient sera of early carcinogenesis [7]. The presence of autoantibodies to TAAs has been described in several tumour types including breast [7-9)] ovarian [10], gastric [11] lung [12]-[15], colorectal [16], pancreatic [17] and oesophageal [18], and may be present years before clinical manifestation of the disease [19]–[23].…”

Principles and Application of Microarray Technology in Thyroid Cancer Research

“…Especially, developments in microarrays for the elucidation of tumour-specific autoantibody profiles have been found to be very useful in enabling diagnostics, and many studies have been published regarding their utility in different (non-cancerous) diseases, as well as in cancer. Table 3 illustrates the potential of this testing principle highlighting "colon cancer" studies (Table 3) (Carpelan-Holmstrom et al, 1995;Ran et al, 2008;Liu et al, 2009;Babel et al, 2009;Chan et al, 2010). To the best of our knowledge, systematic studies using this approach are lacking for thyroid cancer diagnostics, although this approach may enable minimally invasive early diagnostic and even pres-symptomatic screening of patients.…”