Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein: A Novel Biomarker of Breast Cancer Screening and Diagnosis

Yi, Jae Kyo; Chang, Jong Wook; Han, Wonshik; Lee, Jong Won; Ko, Eunyoung; Kim, Dong Hyun; Bae, Ji-Yeon; Yu, Jonghan; Lee, Cheolju; Yu, Myeong-Hee; Noh, Dong‐Young

doi:10.1158/1055-9965.epi-08-0696

Cited by 57 publications

(48 citation statements)

References 44 publications

(35 reference statements)

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“…They are biochemically well-characterized, and many reagents and techniques are available for their detection, simplifying assay development. Until very recently, several specific autoantibodies have been detected in the sera of patients with advanced-stage breast cancer (14,(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58). However, very few studies have attempted to identify and/or evaluate autoantibodies in node-negative earlystage PBC ( 2 cm) or, more importantly, in preinvasive breast cancer, for which mammography's sensitivity is decreased.…”

Section: Discussionmentioning

confidence: 99%

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Lacombe

Mangé

Bougnoux

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Background: The sensitivity of mammography for the detection of small lesions, including node-negative early-stage (T1N0) primary breast cancer (PBC) and ductal carcinoma in situ (DCIS), is significantly decreased in young patients. From a clinical standpoint, an inconclusive mammogram reflects the inability of clinicians to confidently decide whether patients should be referred for biopsy or for follow-up with repeat imaging.Methods: Specific ELISAs were developed for a panel of 13 well-recognized breast autoantigens (HSP60, FKBP52, PRDX2, PPIA, MUC1, GAL3, PAK2, P53, CCNB1, PHB2, RACK1, RUVBL1, and HER2). Circulating autoantibody levels were measured in a cohort of 396 serum samples from histologically confirmed DCIS (n ¼ 87) or T1N0 PBC (n ¼ 153) and healthy controls (n ¼ 156).Results: Individually, antibodies against CCNB1, FKBP52, GAL3, PAK2, PRDX2, PPIA, P53, and MUC1 demonstrated discriminatory power between breast cancer and healthy control groups. At 90% sensitivity, the overall combined specificity of the autoantibody serum screening test was 42%. Adjustment for higher sensitivities of 95% and 99% resulted in 30% and 21% specificities, respectively (33% and 18% in T1N0 PBC and 28% and 21% in DCIS). Finally, in patients with node-negative early-stage breast cancer younger than 50 years, the autoantibody assay exhibited 59% specificity with a fixed sensitivity at 90%.Conclusions: Our autoantibody panel allows accurate detection of early breast cancer and DCIS, notably in younger patients.Impact: Clinical assessment of this autoantibody panel displays a potential to facilitate clinical management of early-stage breast cancer detection in cases of inconclusive mammogram. Cancer Epidemiol Biomarkers Prev; 23(9); 1834-42. Ó2014 AACR.

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Section: Discussionmentioning

confidence: 99%

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Lacombe

Mangé

Bougnoux

et al. 2014

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…78), and NY-ESO-1 (79) were first discovered in patients with breast cancer. In fact, antibodies to HER2/neu (76) have been detected in patients with early-stage breast cancer but their presence has also been detected in other cancers, limiting their use as a diagnostic biomarker for breast cancer alone (28,30,80). An increase to 44% sensitivity and 97.6% specificity in breast cancer detection was achieved through the successive addition of the three TAAs p53, protein 16 (p16), and avian myelocytomatosis viral oncogene homolog (c-myc; ref.…”

Section: Breast Cancermentioning

confidence: 99%

“…The study found HSP60 autoantibodies in 47.5% of patients with breast cancer and in only 4.7% of healthy control sera. a-2-HS-glycoprotein (AHSG) autoantibodies have also been identified in 79.1% of 81 breast cancer patient samples and only in 9.6% of 73 control samples; however, the diagnostic relevance of these autoantibodies remains to be validated (80).…”

Section: Breast 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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“…Major protein depletion, solution isoelectric focusing, and 1D PAGE resulted in 575 and 2,890 protein identifications from plasma and serum, respectively . Identifying the targets of immune reactions to proteins from cancer cells, normal self cells, and bacteria has been greatly facilitated by the use of PAGE followed by immunological probing with patient sera and mass spectrometry (Brichory et al, 2001;Hong et al, 2006;Pereira-Faca et al, 2007;Basagana et al, 2008;Bunk et al, 2008;Desmetz et al, 2008;Fujita et al, 2008;Hamrita et al, 2008;Nagashio et al, 2008;Taylor et al, 2008;Zhong et al, 2008;Kim et al, 2008b;Liu et al, 2008b;Forgber et al, 2009;He et al, 2009;Patwa et al, 2009;Rao et al, 2009;Shimada et al, 2009;Tamesa et al, 2009;Yi et al, 2009). A large number of protein isoforms in serum, or EDTA versus citrated plasma, were detected by fluorescent labeling prior to separation of the intact proteins by charge, hydrophobic character and molecular mass (Misek et al, 2005).…”

Section: E One-dimensional Poly Acrylamide Gel Electrophoresis (1d Pmentioning

confidence: 99%

Mass spectrometry of peptides and proteins from human blood

Zhu

Bowden

Zhang

et al. 2010

Mass Spectrometry Reviews

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It is difficult to convey the accelerating rate and growing importance of mass spectrometry applications to human blood proteins and peptides. Mass spectrometry can rapidly detect and identify the ionizable peptides from the proteins in a simple mixture and reveal many of their post-translational modifications. However, blood is a complex mixture that may contain many proteins first expressed in cells and tissues. The complete analysis of blood proteins is a daunting task that will rely on a wide range of disciplines from physics, chemistry, biochemistry, genetics, electromagnetic instrumentation, mathematics and computation. Therefore the comprehensive discovery and analysis of blood proteins will rank among the great technical challenges and require the cumulative sum of many of mankind's scientific achievements together. A variety of methods have been used to fractionate, analyze and identify proteins from blood, each yielding a small piece of the whole and throwing the great size of the task into sharp relief. The approaches attempted to date clearly indicate that enumerating the proteins and peptides of blood can be accomplished. There is no doubt that the mass spectrometry of blood will be crucial to the discovery and analysis of proteins, enzyme activities, and post-translational processes that underlay the mechanisms of disease. At present both discovery and quantification of proteins from blood are commonly reaching sensitivities of ∼1 ng/mL.

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Autoantibody to Tumor Antigen, Alpha 2-HS Glycoprotein: A Novel Biomarker of Breast Cancer Screening and Diagnosis

Cited by 57 publications

References 44 publications

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

A Multiparametric Serum Marker Panel as a Complementary Test to Mammography for the Diagnosis of Node-Negative Early-Stage Breast Cancer and DCIS in Young Women

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Mass spectrometry of peptides and proteins from human blood

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