Biomarker research with prospective study designs for the early detection of cancer

Pesch, Beate; Brüning, Thomas; Johnen, Georg; Casjens, Swaantje; Bonberg, Nadine; Taeger, Dirk; Müller, Annette; Weber, Daniel G.; Behrens, Thomas

doi:10.1016/j.bbapap.2013.12.007

Cited by 47 publications

(66 citation statements)

References 72 publications

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“…A major goal of our development of markers is the future application in the screening of high-risk populations, e.g., former asbestos workers. Besides being able to detect early stages of cancer, a very high specificity is an important requirement for markers in order to avoid false-positive results that could cause unnecessary psychological burden for the participants of the screening program [30]. We therefore calculated the sensitivity of the markers for different cutoffs conditional on a specificity of at least 95%.…”

Section: Discussionmentioning

confidence: 99%

“…We recruited the controls from the target population of asbestos-exposed subjects, which constitute a more challenging control group than the general population. However, a nested case-control study would be the preferred design [30, 44]. We currently conduct a prospective study in asbestos-exposed subject that may serve for the validation of calretinin, mesothelin, and other markers to detect MM.…”

Section: Discussionmentioning

confidence: 99%

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Calretinin as a blood-based biomarker for mesothelioma

et al. 2017

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BackgroundMalignant mesothelioma (MM) is a deadly cancer mainly caused by previous exposure to asbestos. With a latency period up to 50 years the incidence of MM is still increasing, even in countries that banned asbestos. Secondary prevention has been established to provide persons at risk regular health examinations. An earlier detection with tumor markers might improve therapeutic options. Previously, we have developed a new blood-based assay for the protein marker calretinin. Aim of this study was the verification of the assay in an independent study population and comparison with the established marker mesothelin.MethodsFor a case-control study in men, a total of 163 cases of pleural MM and 163 controls were available from Australia, another 36 cases and 72 controls were recruited in Germany. All controls had asbestosis and/or plaques. Calretinin and mesothelin were determined by ELISA (enzyme-linked immunosorbent assay) in serum or plasma collected prior to therapy. We estimated the performance of both markers and tested factors potentially influencing marker concentrations like age, sample storage time, and MM subtype.ResultsCalretinin was able to detect all major subtypes except for sarcomatoid MM. Calretinin showed a similar performance in Australian and German men. At a pre-defined specificity of 95% the sensitivity of calretinin reached 71% and that of mesothelin 69%, when excluding sarcomatoid MM. At 97% specificity, the combination with calretinin increased the sensitivity of mesothelin from 66% to 75%. Sample storage time did not influence the results. In controls the concentrations of calretinin increased 1.87-fold (95% CI 1.10–3.20) per 10 years of age and slightly more for mesothelin (2.28, 95% CI 1.30–4.00).ConclusionsCalretinin could be verified as a blood-based marker for MM. The assay is robust and shows a performance that is comparable to that of mesothelin. Retrospective analyses would not be limited by storage time. The high specificity supports a combination of calretinin with other markers. Calretinin is specific for epithelioid and biphasic MM but not the rarer sarcomatoid form. Molecular markers like calretinin and mesothelin are promising tools to improve and supplement the diagnosis of MM and warrant further validation in a prospective study.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3375-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Calretinin as a blood-based biomarker for mesothelioma

et al. 2017

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“…Additionally, to assess the feasibility of miR-132-3p and miR-126 to detect the cancer at early stages, studies with a prospective design are urgently needed [7]. Regarding malignant mesothelioma, the prospective study MoMar started in 2008 comprising more than 2,000 German workers formerly exposed to asbestos.…”

Section: Discussionmentioning

confidence: 99%

Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma

et al. 2017

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The use of circulating microRNAs as biomarkers has opened new opportunities for diagnosis of cancer because microRNAs exhibit tumor-specific expression profiles. The aim of this study was the identification of circulating microRNAs in human plasma as potential biomarkers for the diagnosis of malignant mesothelioma. For discovery, TaqMan Low Density Array Human MicroRNA Cards were used to analyze 377 microRNAs in plasma samples from 21 mesothelioma patients and 21 asbestos-exposed controls. For verification, individual TaqMan microRNA assays were used for quantitative real-time PCR in plasma samples from 22 mesothelioma patients and 44 asbestos-exposed controls. The circulating miR-132-3p showed different expression levels between mesothelioma patients and asbestos-exposed controls. For discrimination, sensitivity of 86% and specificity of 61% were calculated. Circulating miR-132-3p in plasma was not affected by hemolysis and no impact of age or smoking status on miR-132-3p levels could be observed. For the combination of miR-132-3p with the previously described miR-126, sensitivity of 77% and specificity of 86% were calculated. The results of this study indicate that miR-132-3p might be a new promising diagnostic biomarker for malignant mesothelioma. It is indicated that the combination of miR-132-3p with other individual biomarkers improves the biomarker performance.

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“…The latter is particularly true for samples requiring invasive sample collection procedures (e.g., biopsies) and is even worse for samples from healthy donors (control samples) (Pesch et al, 2014). Moreover, patient samples are normally limited to one time point and they do not offer the opportunity for a controlled interventional study.…”

Section: Introductionmentioning

confidence: 99%

PeptideManager: a peptide selection tool for targeted proteomic studies involving mixed samples from different species

Demeure¹,

Duriez²,

Domon³

et al. 2014

Front. Genet.

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The search for clinically useful protein biomarkers using advanced mass spectrometry approaches represents a major focus in cancer research. However, the direct analysis of human samples may be challenging due to limited availability, the absence of appropriate control samples, or the large background variability observed in patient material. As an alternative approach, human tumors orthotopically implanted into a different species (xenografts) are clinically relevant models that have proven their utility in pre-clinical research. Patient derived xenografts for glioblastoma have been extensively characterized in our laboratory and have been shown to retain the characteristics of the parental tumor at the phenotypic and genetic level. Such models were also found to adequately mimic the behavior and treatment response of human tumors. The reproducibility of such xenograft models, the possibility to identify their host background and perform tumor-host interaction studies, are major advantages over the direct analysis of human samples. At the proteome level, the analysis of xenograft samples is challenged by the presence of proteins from two different species which, depending on tumor size, type or location, often appear at variable ratios. Any proteomics approach aimed at quantifying proteins within such samples must consider the identification of species specific peptides in order to avoid biases introduced by the host proteome. Here, we present an in-house methodology and tool developed to select peptides used as surrogates for protein candidates from a defined proteome (e.g., human) in a host proteome background (e.g., mouse, rat) suited for a mass spectrometry analysis. The tools presented here are applicable to any species specific proteome, provided a protein database is available. By linking the information from both proteomes, PeptideManager significantly facilitates and expedites the selection of peptides used as surrogates to analyze proteins of interest.

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Biomarker research with prospective study designs for the early detection of cancer

Cited by 47 publications

References 72 publications

Calretinin as a blood-based biomarker for mesothelioma

Calretinin as a blood-based biomarker for mesothelioma

Circulating miR-132-3p as a Candidate Diagnostic Biomarker for Malignant Mesothelioma

PeptideManager: a peptide selection tool for targeted proteomic studies involving mixed samples from different species

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