Autoantibodies in breast cancer: their use as an aid to early diagnosis

Chapman, Caroline; Murray, Andrea; Chakrabarti, Jayeta; Thorpe, Alison; Woolston, Caroline M.; Şahin, Uğur; Barnes, Anthony; Robertson, J. F. R.

doi:10.1093/annonc/mdm007

Cited by 233 publications

(233 citation statements)

References 13 publications

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“…Response rates to single antigens in this population ranged from 3% to 34%, but response rates for healthy controls were not reported. 50 Although preliminary, these data support further investigation to develop a multiplexed serum antibody based assays for breast cancer diagnosis.…”

Section: Detecting Serum Antibody Response To a Panel Of Taasmentioning

confidence: 60%

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

2008

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Over the past decade, it has been demonstrated that cancer is immunogenic, and multiple tumor antigens have been identified in cancer patients. It is now possible to potentially harness the immune response elicited by cancer growth as a potential diagnostic tool. Humoral immunity, or the development of autoantibodies against tumor-associated proteins, may be used as a marker for cancer exposure. Unlike circulating proteins that are shed by bulky tumors, serum autoantibodies are detectable even when antigen expression is minimal. This paper will review the methods used for tumor antigen discovery and overview what is known about autoantibodies targeting common cancer antigens with a focus on breast cancer. Data will be presented modeling the use of tumor antigen associated autoantibodies as a breast cancer diagnostic. The endogenous humoral immune response present in cancer patients may allow the identification of individuals exposed to the malignant transformation of somatic cells.

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Section: Detecting Serum Antibody Response To a Panel Of Taasmentioning

confidence: 60%

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

2008

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“…Similar publications on other single autoantibodies (39-41) also indicate the induction of autoantibodies happening relatively early in the process of carcinogenesis. Autoantibodies to a panel of cancer-associated antigetns have been reported up (32) in lung cancer and up to 4 years before screening mammography detected breast cancers in young women at increased risk (31,33). A recent presentation on SCLC has shown that EarlyCDT-Lung was positive in prediagnostic samples between 1 and 49 months prior to diagnosis of SCLC (42).…”

Section: Discussionmentioning

confidence: 99%

EarlyCDT-Lung: An Immunobiomarker Test as an Aid to Early Detection of Lung Cancer

Lam

Boyle

Healey

et al. 2011

Cancer Prevention Research

128

100

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Recent publications have reported the technical and clinical validation of EarlyCDT-Lung, an autoantibody test which detected elevated autoantibodies in 40% of lung cancers at diagnosis. This manuscript reports the results of EarlyCDT-Lung run on four new (postvalidation) data sets. The following four cohorts of patients (n ¼ 574) with newly diagnosed lung cancer were identified: group 1 (n ¼ 122), 100% small cell lung cancer (SCLC); group 2 (n ¼ 249), 97% non-small cell lung cancer (NSCLC); group 3 (n ¼ 122), 100% NSCLC; group 4 (n ¼ 81), 62% NSCLC. Serum samples were obtained after diagnosis, prior to any anticancer treatment. Autoantibody levels were measured against a panel of six tumor-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1, and SOX2) in the EarlyCDT-Lung panel and previously established cutoffs applied. In groups 2, 3, and 4, patients were individually matched by gender, age, and smoking history to a control individual with no history of malignant disease. Assay sensitivity was tested in relation to cancer type and stage, and in the matched normals to demographic variables. The autoantibody panel showed sensitivity/specificity of 57%/n.d (not done) for SCLC in group 1, 34%/87% for NSCLC in group 2, 31% and 84% for NSCLC in group 3, and 35%/89% for NSCLC and 43%/89% for SCLC in group 4. There was no significant difference in positivity of EarlyCDT-Lung and different lung cancer stages. These studies confirm the value of an autoantibody assay, EarlyCDT-Lung, as an aid to detecting lung cancer in patients at high risk of the disease. Cancer Prev Res; 4(7); 1126-34. Ó2011 AACR.

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“…Self-proteins (autoantigens) altered before or during tumor formation can elicit an immune response (13)(14)(15)(16)(17)(18)(19). These tumor-specific autoantibodies can be detected at early cancer stages and prior to cancer diagnosis revealing a great potential as biomarkers (14,15,20). Tumor proteins can be affected by specific point mutations, misfolding, overexpression, aberrant glycosylation, truncation, or aberrant degradation (e.g.…”

Section: Colorectal Cancer (Crc)mentioning

confidence: 99%

Identification of Tumor-associated Autoantigens for the Diagnosis of Colorectal Cancer in Serum Using High Density Protein Microarrays

Babel

Barderas

Dı́az-Uriarte

et al. 2009

Molecular & Cellular Proteomics

146

143

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There is a mounting evidence of the existence of autoantibodies associated to cancer progression. Antibodies are the target of choice for serum screening because of their stability and suitability for sensitive immunoassays. By using commercial protein microarrays containing 8000 human proteins, we examined 20 sera from colorectal cancer (CRC) patients and healthy subjects to identify autoantibody patterns and associated antigens. Fortythree proteins were differentially recognized by tumoral and reference sera (p value <0.04) in the protein microarrays. Five immunoreactive antigens, PIM1, MAPKAPK3, STK4, SRC, and FGFR4, showed the highest prevalence in cancer samples, whereas ACVR2B was more abundant in normal sera. Three of them, PIM1, MAPKAPK3, and ACVR2B, were used for further validation. A significant increase in the expression level of these antigens on CRC cell lines and colonic mucosa was confirmed by immunoblotting and immunohistochemistry on tissue microarrays. A diagnostic ELISA based on the combination of MAPKAPK3 and ACVR2B proteins yielded specificity and sensitivity values of 73.9 and 83.3% (area under the curve, 0.85), respectively, for CRC discrimination after using an independent sample set containing 94 sera representative of different stages of progression and control subjects. In summary, these studies confirmed the presence of specific autoantibodies for CRC and revealed new individual markers of disease (PIM1, MAPKAPK3, and ACVR2B) with the potential to diagnose CRC with higher specificity and sensitivity than previously reported serum biomarkers. Molecular & Cellular Proteomics 8:2382-2395, 2009.

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Autoantibodies in breast cancer: their use as an aid to early diagnosis

Cited by 233 publications

References 13 publications

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

Humoral Immunity Directed against Tumor-Associated Antigens As Potential Biomarkers for the Early Diagnosis of Cancer

EarlyCDT-Lung: An Immunobiomarker Test as an Aid to Early Detection of Lung Cancer

Identification of Tumor-associated Autoantigens for the Diagnosis of Colorectal Cancer in Serum Using High Density Protein Microarrays

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