Technical validation of an autoantibody test for lung cancer

Murray, Andrea; Chapman, Caroline; Healey, Graham F.; Peek, Laura J.; Parsons, Grace F.; Baldwin, David R; Barnes, Anthony; Sewell, Herb F.; Fritsche, Herbert A.; Robertson, J. F. R.

doi:10.1093/annonc/mdp606

Cited by 71 publications

(104 citation statements)

References 16 publications

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“…Serum samples were evaluated in the EarlyCDT-Lung assay for autoantibodies against p53, NY-ESO-1, CAGE, GBU4-5 (also known as FLI3072 or TDRD12), Annexin 1, and SOX2, as previously reported (1,2). For each group, samples from patients with cancers, matched normals, and control sera for the assay were interspersed: samples were assayed in an order so that any batch effects would be spread over all sample types.…”

Section: Patientsmentioning

confidence: 99%

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

Lam

Boyle

Healey

et al. 2011

Cancer Prevention Research

126

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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Section: Patientsmentioning

confidence: 99%

“…Color formation was allowed to proceed for 15 minutes before the optical density of each well was determined spectrophotometrically at 650 nm. The assay included a calibration system which utilized fluids drained from pleural or peritoneal cavities of patients with lung cancer, producing calibrated reference units (1).…”

Section: Autoantibody Assaymentioning

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

126

100

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“…detects the presence of TA autoantibodies to a panel of seven lung cancer associated antigens using an indirect enzyme-linked immunosorbent assay (ELISA) method [10] [11]. A sample is positive when at least one of the panel of TA autoantibodies is elevated above a pre-determined cut-off [12].…”

Section: Introductionmentioning

confidence: 99%

“…A sample is positive when at least one of the panel of TA autoantibodies is elevated above a pre-determined cut-off [12]. The test has been both technically [10] and clinically validated in seven independent validation cohorts [11] [13] including highrisk control groups matched for age, sex, and smoking history. The performance characteristics have been further validated in the commercial setting by an audit of clinical outcomes for the first 1599 patients who had a valid EarlyCDT-Lung and unknown nodule status [14].…”

Section: Introductionmentioning

confidence: 99%

Tumor-Associated Autoantibodies: Re-Optimization of EarlyCDT-Lung Diagnostic Performance and Its Application to Indeterminate Pulmonary Nodules

Healey¹,

Macdonald²,

Reynolds³

et al. 2017

JCT

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Background: Low-dose computed tomography (CT) screening reduces lung cancer mortality but costs are prohibitive for most healthcare budgets due to high false positive rates. An adjunctive test able to distinguish malignant from benign pulmonary nodules would be hugely beneficial. EarlyCDT-Lung measures serum autoantibodies to tumor-associated antigens and has found clinical acceptance to aid early detection of lung cancer for high risk patients. However performance was optimized for screening. The construction of a receiver-operating characteristic (ROC) curve would enable optimization of performance for alternative settings, including nodule malignancy. Methods: A Monte-Carlo search method was used to construct a ROC curve using a case-control cohort, enabling high and low specificity versions of EarlyCDT-Lung to be determined. These were used for a theoretical evaluation of a nodule cohort, and positive predictive value (PPV) was calculated under the assumption of independence of risk source. Patients or their nodules are typically classified into three risk groups: low (0% -10%), intermediate (10% -65%) and high (>65%) risk of malignancy. The predicted shift in risk group by application of the high and low specificity versions, along with the current commercial EarlyCDT-Lung, was then estimated. Results: The ROC curve, with an area under the curve of 0.743, was constructed. The high specificity (98%), low specificity (49%) and current commercial (91% specificity) versions of EarlyCDT-Lung re-classified 27%, 23% and 26% of intermediate nodules, respectively, to either a higher (10%, 8% and 10%) or lower (17%, 15% and 16%) risk group. Conclusion: A ROC curve was constructed to allow performance prediction of EarlyCDT-Lung at different specificities in the indeterminate nodule setting. This enabled risk re-classification of intermediate risk nodules, and could therefore facilitate alternative more appropriate inHow to cite this paper:

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“…The validation of these novel lung cancer autoantibodies mandated the development of robust detection assays that are sensitive, reproducible, and high throughput. To test the utility of autoantibodies as a diagnostic tool for lung cancer, indirect ELISA tests were developed and validated for a panel of six known lung cancer TAAs (p53, NY-ESO-1, cancerassociated antigen, GBU4-5, Annexin 1, and SOX2) (54,55). These efforts yielded an assay with high reproducibility, precision, and linearity that was able to identify nearly 40% of primary lung cancers via a peripheral blood test.…”

Section: Circulating Autoantibodiesmentioning

confidence: 99%

Advances in Proteomic Strategies toward the Early Detection of Lung Cancer

Hassanein¹,

Rahman²,

Chaurand³

et al. 2011

Proceedings of the American Thoracic Society

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TennesseeSince the advent of the new proteomics era more than a decade ago, large-scale studies of protein profiling have been exploited to identify the distinctive molecular signatures in a wide array of biological systems spanning areas of basic biological research, various disease states, and biomarker discovery directed toward therapeutic applications. Recent advances in protein separation and identification techniques have significantly improved proteomics approaches, leading to enhancement of the depth and breadth of proteome coverage. Proteomic signatures specific for invasive lung cancer and preinvasive lesions have begun to emerge. In this review we provide a critical assessment of the state of recent advances in proteomic approaches and the biological lessons they have yielded, with specific emphasis on the discovery of biomarker signatures for the early detection of lung cancer.Keywords: proteomics; biomarker; early detection; lung cancer CHALLENGES IN LUNG CANCER RESEARCHLung cancer is the deadliest cancer in the United States and worldwide, accounting for 15% of all cancer incidence and 29% of all cancer deaths, with a 5-year survival rate of only 15% (1, 2). Lung cancer represents a spectrum of diseases with tremendous heterogeneity at the pathological and molecular levels (3-6) that is strongly associated with smoking as a risk factor. With about 20% of the United States adult population smoking and 1 billion smokers worldwide, it was estimated that in 2009 lung cancer claimed more lives than breast, prostate, colon, liver, kidney, and melanoma cancers combined (2, 7). Despite the recent improvements of bronchoscopic and surgical techniques as well as advances in chemotherapy and radiation therapy treatments, attempts to improve patient outcomes are faced with immense challenges. Several noninvasive detection technologies have been investigated. Imaging techniques, such as chest radiography, lowdose spiral computed tomography, sputum cytology, and molecular biomarkers in various biological samples, have been tested for their diagnostic value for early detection of lung cancer (8, 9). Although these tests vary in their sensitivity and specificity, only low-dose chest computed tomography was shown to reduce lung cancer-specific mortality (10-12). This encouraging finding calls for new molecular strategies to address the noninvasive diagnostic and risk assessment for lung cancer. These molecular strategies will have to demonstrate clinical utility and may complement currently tested strategies. NATURAL HISTORY OF LUNG CANCER PROGRESSION AND A WINDOW FOR EARLY DETECTIONLung cancer can be considered to result from a long history of repeated airway damage and repair cycles. Although clinically addressed at the time of diagnosis, the disease process develops for months and years before affecting patients' lives. This rather long disease process (Figure 1) represents a window of opportunity where the intervention should take place with the aim of preventing the development of disease (e.g., primary preven...

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Technical validation of an autoantibody test for lung cancer

Cited by 71 publications

References 16 publications

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

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

Tumor-Associated Autoantibodies: Re-Optimization of EarlyCDT-Lung Diagnostic Performance and Its Application to Indeterminate Pulmonary Nodules

Advances in Proteomic Strategies toward the Early Detection of Lung Cancer

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