Autoantibodies in lung cancer: possibilities for early detection and subsequent cure

Chapman, Caroline; Murray, Andrea; McElveen, Jane; Şahin, Uğur; Luxemburger, Ulrich; Türeci, Özlem; Wiewrodt, Rainer; Barnes, Anthony; Robertson, J. F. R.

doi:10.1136/thx.2007.083592

Cited by 201 publications

(184 citation statements)

References 34 publications

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“…When a-enolase was used in combination with other potential autoantibody biomarkers such as CEA and cytokeratin fragment 21-1 (CYFRA 21-1) in a cohort of 94 patients with non-small cell lung cancer, 15 patients with small cell lung cancer, 10 patients with gastric cancer, 8 patients with colon cancer, 9 patients with Myobacterium avium complex infection of the lung, and 60 healthy controls, the sensitivity of this potential diagnostic lung cancer biomarker panel was calculated to be as high as 69.3% with a specificity 98.3% (90). An ELISA panel of potential diagnostic lung cancer autoantibody biomarkers composed of p53, c-myc, Her-2, NY-ESO-1, MUC1, cancer antigen 1 (CAGE), and TAA GBU4-5 (GBU4-5) tested by Chapman and colleagues yielded promising results of 76% sensitivity and 92% specificity in another cohort consisting of 82 patients with non-small cell lung cancer, 22 patients with small cell lung cancer, and 50 healthy controls (91).…”

Section: Lung Cancermentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

130

107

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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: Lung Cancermentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

130

107

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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

145

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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“…Recombinant proteins were obtained for each of the candidate autoantibodies identified in the proteomic discovery efforts having value for NSCLC detection (see Table 2) as well as for a second group of autoantibodies with documented value for our purpose, including NY-ESO (13-15), p53 (13,(16)(17)(18)(19)(20)(21), peroxiredoxin (22,23), triosephosphate isomerase (23), recoverin (24), 3-oxoacid CoA transferase (23), survivin (also known as BIRC5; ref. 25), c-Myc (13,26), Annexin II (27), and ubiquillin (28). Commercial antibodies (as used above for target confirmation) were obtained for these targets to serve as positive controls during assay performance.…”

Section: Serum Test Developmentmentioning

confidence: 99%

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

Farlow

Patel

Basu

et al. 2010

Clinical Cancer Research

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Purpose: Non-small cell lung cancer (NSCLC) has an overall 5-year survival of <15%; however, the 5-year survival for stage I disease is over 50%. Unfortunately, 75% of NSCLC is diagnosed at an advanced stage not amenable to surgery. A convenient serum assay capable of unambiguously identifying patients with NSCLC may provide an ideal diagnostic measure to complement computed tomography-based screening protocols.Experimental Design: Standard immunoproteomic method was used to assess differences in circulating autoantibodies among lung adenocarcinoma patients relative to cancer-free controls. Candidate autoantibodies identified by these discovery phase studies were translated into Luminex-based "direct-capture" immunobead assays along with 10 autoantigens with previously reported diagnostic value. These assays were then used to evaluate a second patient cohort composed of four discrete populations, including: 117 NSCLC (81 T 1-2 N 0 M 0 and 36 T 1-2 N 1-2 M 0 ), 30 chronic obstructive pulmonary disorder (COPD)/ asthma, 13 nonmalignant lung nodule, and 31 "normal" controls. Multivariate statistical methods were then used to identify the optimal combination of biomarkers for classifying patient disease status and develop a convenient algorithm for this purpose.Results: Our immunoproteomic-based biomarker discovery efforts yielded 16 autoantibodies differentially expressed in NSCLC versus control serum. Thirteen of the 25 analytes tested showed statistical significance (Mann-Whitney P < 0.05 and a receiver operator characteristic "area under the curve" over 0.65) when evaluated against a second patient cohort. Multivariate statistical analyses identified a six-biomarker panel with only a 7% misclassification rate.Conclusions: We developed a six-autoantibody algorithm for detecting cases of NSCLC among several high-risk populations. Population-based validation studies are now required to assign the true value of this tool for identifying early-stage NSCLC. Clin Cancer Res; 16(13); 3452-62. ©2010 AACR.Lung cancer remains the leading cause of cancer death nationwide, with ∼160,000 deaths predicted in the United States in 2009 (1). Non-small cell lung cancer (NSCLC) accounts for 80% of all lung cancers and has a poor overall 5-year survival rate of ∼15% (2-4). This low survival rate is largely attributed to the fact that >75% of patients present with local or distant metastasis at diagnosis, which are associated with a 21% and 3% 5-year survival, respectively (2,3,5). In contrast to these dismal figures, stage I disease is associated with a 50% to 67% 5-year survival but accounts for only 15% of patients (2). This suggests that if patients could be diagnosed at an earlier stage, when a complete surgical resection offers the greatest potential for a cure, the mortality associated with this disease could be reduced.To that end, considerable efforts have been undertaken to produce an effective screening method for early NSCLC. In the 1950s, trials of chest X-rays alone or in combination with sputum analysis were com...

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Autoantibodies in lung cancer: possibilities for early detection and subsequent cure

Cited by 201 publications

References 34 publications

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

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

Development of a Multiplexed Tumor-Associated Autoantibody-Based Blood Test for the Detection of Non–Small Cell Lung Cancer

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