Cancer-associated antigens and antigen arrays in serological diagnostics of malignant tumors

Belousov, Pavel V.; Kuprash, Dmitry V.; Sazykin, Alexey Y.; Khlgatian, Svetlana V.; Penkov, Dmitry; Shebzukhov, Yu. V.; Nedospasov, Sergei A.

doi:10.1134/s000629790805009x

Cited by 13 publications

(12 citation statements)

References 74 publications

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“…Studies have shown that autoantibodies to p53 can help identify individuals at increased risk of developing colorectal cancer as these autoantibodies have been detected in patients with precancerous colorectal cancer lesions. In fact, the screening for these autoantibodies is suggested in addition to colonoscopy screens (95)(96)(97). However, antibodies to p53 have also been associated with a range of other cancers, which reduces the specificity of this biomarker for colon cancer.…”

Section: Colon Cancermentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

134

111

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Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely a-2-HS-glycoprotein and des-g-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. Cancer Epidemiol Biomarkers Prev; 22(12); 2161-81. Ó2013 AACR.

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Section: Colon Cancermentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

134

111

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“…serum antibody | biomarkers | protein microarrays | serology | autoantigen P rotein microarrays allow for the detection of specific serum antibodies against a very large number of targets simultaneously. Arrays can be used with high throughput to determine patterns of antigens recognized by autoantibodies during the course of diseases, such as autoimmunity or cancer (1)(2)(3)(4)(5)(6)(7)(8)(9), as well as a way to characterize the repertoire of serological responses in healthy individuals (10). Defined protein collections assembled from phage expression systems or purified from recombinant sources were used to detect antibody responses in the serum of ovarian (11,12), breast (13), colorectal (2), pancreatic (14), or lung (15,16) cancer patients, and some of these responses appear to have diagnostic significance.…”

mentioning

confidence: 99%

Seromic profiling of ovarian and pancreatic cancer

Gnjatic

Ritter

Büchler³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

163

142

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Autoantibodies, a hallmark of both autoimmunity and cancer, represent an easily accessible surrogate for measuring adaptive immune responses to cancer. Sera can now be assayed for reactivity against thousands of proteins using microarrays, but there is no agreed-upon standard to analyze results. We developed a set of tailored quality control and normalization procedures based on ELISA validation to allow patient comparisons and determination of individual cutoffs for specificity and sensitivity. Sera from 60 patients with pancreatic cancer, 51 patients with ovarian cancer, and 53 age-matched healthy donors were used to assess the binding of IgG antibodies against a panel of >8000 human antigens using protein microarrays and fluorescence detection. The resulting data interpretation led to the definition and ranking of proteins with preferred recognition by the sera from cancer patients in comparison with healthy donors, both by frequency and strength of signal. We found that 202 proteins were preferentially immunogenic in ovarian cancer sera compared to 29 in pancreatic cancer, with few overlaps. Correlates of autoantibody signatures with known tumor expression of corresponding antigens, functional pathways, clinical stage, and outcome were examined. Serological analysis of arrays displaying the complete human proteome (seromics) represents a new era in cancer immunology, opening the way to defining the repertoire of the humoral immune response to cancer. serum antibody | biomarkers | protein microarrays | serology | autoantigen

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“…Patel et al went even further to develop an autoantibody "direct-capture" immunobead assay using selected antigens for successful detection of nonsmall-cell lung carcinoma with a sensitivity and specificity of 94% and 97%, respectively (Patel et al, 2011). Similar advances using panels of autoantibodies have been made for the diagnosis of colon cancer (Belousov et al, 2008;Chen et al, 2007;Cioffi et al, 2004;Yoshizawa et al, 2007), stomach cancer (di Mario & Cavallaro, 2008), and hepatocellular carcinoma (Li, Chen, Yu, Li, & Wang, 2008;Marrero et al, 2003). Studies have demonstrated that the successful development of a single autoantibody biomarker approach for disease diagnostics has so far been hampered by low sensitivity, specificity, and predictive values, as well as poor reproducibility in larger sample cohorts.…”

Section: Autoantibodies In Cancer: Byproduct or Biomarker?mentioning

confidence: 98%