Challenges in planning and conducting diagnostic studies with molecular biomarkers

Antibodies against tumor-associated antigens have been found in serum of patients with various types of cancers and may serve as biomarkers for early detection of gastric cancer as well. This systematic review aims to give an overview about known autoantibodies and their diagnostic value in gastric cancer. We conducted a systematic literature search in two databases to identify studies which performed serological testing for autoantibodies in gastric cancer patients and controls. Data on study characteristics and results were extracted independently by two reviewers. Overall, 39 articles reporting the detection of 34 different autoantibodies met the inclusion criteria for this review. The most common antibody detection method was enzymelinked immunosorbent assay and the most frequently assessed autoantibody was anti-p53, which was tested in 13 studies. Most antibodies were assessed in only one study and only few authors have evaluated the diagnostic value of combinations of multiple autoantibodies. For single autoantibodies, specificity was generally very high (median: 99.15%), but sensitivity was mostly rather low (median: 12.35%). For some autoantibody combinations, substantially higher sensitivity at reasonably high levels of specificity could be achieved. Development of extended and optimized multimarker panels of autoantibodies might be a promising approach for gastric cancer early detection.Gastric cancer is the fourth most common cancer and the second most common cause of cancer-related death worldwide.

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“…According to the criteria described by Ziegler et al . all studies are Phase I and Phase II diagnostic or prognostic studies.…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, in many studies the cutoff was chosen post hoc based on the results for the control group (see Supporting Information Table S1). This might lead to overoptimistic results . To ensure valid results the positivity threshold should be defined in an independent training set as it was done by Zayakin et al .…”

Section: Discussionmentioning

confidence: 99%

Systematic review: Serum autoantibodies in the early detection of gastric cancer

Werner

Chen

Tao

et al. 2014

Intl Journal of Cancer

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“…Typically, the threshold that was used was either 2 or 3 SD above the average response in the normal population [7]. Nevertheless, as the cut-off was chosen post hoc based on the results for the control group, this approach could lead to overoptimistic results [106]. To ensure valid results, the positive threshold should be defined based on an independent training dataset, and complete ROC curves should be reported rather than pairs of sensitivity and specificity for only a single specific cut point [107].…”

Section: Discussionmentioning

confidence: 99%

Tumour‐Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta‐Analysis

et al. 2016

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Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a metaanalysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice.

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“…The National Institutes of Health Biomarkers Working Group has defined a biological marker (short biomarker) as “a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention” [3, 4•]. Biomarkers may be laboratory tests, imaging, or other physiological tests, such as body temperature.…”

Section: What Is a Good Biomarker?mentioning

confidence: 99%

“…Biomarkers are essential for the implementation of personalized medicine. Characteristics of high-quality biomarkers are as follows: [1••] they should be noninvasive, easily measured, and economical and produce rapid results; [2] they should be from readily available sources, such as blood or urine; [3] they should have a high sensitivity, allowing early detection, and no overlap in values between diseased patients and healthy controls; [4•] they should have a high specificity, being greatly upregulated (or downregulated) specifically in the diseased samples and unaffected by comorbid conditions; [5] their levels should vary rapidly in response to treatment; [6] their levels should aid in risk stratification and possess prognostic value in terms of real outcomes; and [7] they should be biologically plausible and provide insight into the underlying disease mechanism [5–7]. …”

Section: What Is a Good Biomarker?mentioning

confidence: 99%

Biomarkers for Childhood-Onset Systemic Lupus Erythematosus

Abulaban

Brunner

2014

Curr Rheumatol Rep

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Childhood-onset systemic lupus erythematosus (cSLE) is a systemic autoimmune disease characterized by the presence of autoantibodies. cSLE often affects multiple organs in the body and is known to have a poorer prognosis than adult-onset disease (Azevedo et al. 2014). Current laboratory tests are clearly insufficient for identifying and monitoring the disease. Recent studies have yielded novel biomarkers for cSLE which can be used for monitoring disease activity and response to treatment. The most encouraging biomarkers will be discussed herein and include cell-bound complement activation products, some genomic profiles, and urinary proteins such as neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and others. Previous studies suggested that a combination of the novel biomarkers might help to enhance sensitivity and specificity for early diagnosis, disease monitoring, and prediction of cSLE flares.

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Challenges in planning and conducting diagnostic studies with molecular biomarkers

Cited by 6 publications

References 45 publications

Systematic review: Serum autoantibodies in the early detection of gastric cancer

Systematic review: Serum autoantibodies in the early detection of gastric cancer

Tumour‐Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta‐Analysis

Biomarkers for Childhood-Onset Systemic Lupus Erythematosus

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