Proteomic Analyses of Serial Prediagnostic PLCO Serum in Cases and Controls to Identify Early Detection Ovarian Cancer Biomarkers Rising in a Substantial Fraction of Cases and Stable in Most Controls
对病例和对照中的系列诊断前 PLCO 血清进行蛋白质组学分析,以识别早期检测卵巢癌生物标志物,这些生物标志物在大部分病例中上升,而在大多数对照中保持稳定
基本信息
- 批准号:10703252
- 负责人:
- 金额:$ 12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-15 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:Acute-Phase ProteinsAgeAlgorithmsBehaviorBiologicalBiological AssayBiological MarkersBlood ProteinsBlood specimenCA-125 AntigenCancer EtiologyCell divisionConsumptionCustomDataDetectionDiagnosisDiagnosticDiseaseEarly DiagnosisEarly identificationGoalsGrowthHigh Risk WomanInflammationInvestigationLightLongitudinal StudiesMalignant NeoplasmsMalignant neoplasm of ovaryMeasuresModelingPatternPerformancePersonsPilot ProjectsPlasmaPlasma ProteinsProbabilityProcessProteinsProteomicsResourcesSamplingScreening for Ovarian CancerSerumSignal TransductionSpecificityStatistical ModelsSymptomsTechnologyTest ResultTestingTimeValidationVariantWFDC2 geneWomanarmbiobankbiomarker discoverybiomarker identificationblood-based biomarkercancer biomarkerscancer diagnosiscandidate markercohortdetection sensitivityearly detection biomarkerslongitudinal analysismortalitynew technologynovelprogramsprotein biomarkersresponsescreeningtumortwo-dimensional
项目摘要
Project Summary
This project aims to discover and validate plasma biomarkers for the early detection of ovarian cancer. A
hallmark of cancer is uncontrolled cell division, leading to a doubling time of the tumor. This exponential growth
stands in stark contrast to the stable or slowly changing profile of plasma proteins in almost all other diseases
or in healthy subjects. This project will leverage this unique hallmark to discover and validate plasma protein
biomarkers for the early detection of ovarian cancer. We will discover early detection (ED) plasma protein
biomarkers by identifying the proteins that significantly rise over time in an exponential fashion in a substantial
fraction of cases and yet remain relatively stable over time in most controls. This requires plasma assays over
a large suite of proteins with CVs lower than the protein's biological variation over time which can be as low as
a CV of 10%. Furthermore, a low volume requirement is essential for access to precious biospecimens formed
from long-term large early detection trials. Olink AB has developed proximity extension assays (PEAs) for a
suite of ~1,500 proteins with CVs ranging from 6-12% and with a minimal volume requirement of
3 µL. Applying the Olink proteomic assays to serial pre-diagnostic plasma from subjects in the PLCO who were
diagnosed with ovarian cancer during the study (cases n=50) and to serial plasma samples from a 4:1
matched control (n=200) : case (n=50) cohort will provide longitudinal data on ~1,500 plasma proteins from
cases and controls by which to identify ED candidate biomarkers. Prior to cancer developing in each case, a
biomarker will be stable over time, while after cancer inception the biomarker will rise exponentially reflecting
tumor doubling. This behavior is represented by a change-point model in cases while the same biomarker in
women without ovarian cancer (controls) will have a flat profile. ED biomarkers will be the proteins which have
a change-point in a substantial fraction of cases while remaining stable in most (98%) controls. We will identify
the top 20 ED biomarkers where the criteria for inclusion is a combination of fraction of cases, complementarity
to proteins already selected, and time of rise with earlier risers having priority. After identification of the 20 ED
biomarkers, Olink will develop a custom panel of 20 ED markers with absolute quantification. The custom
panel will assay the same PLCO plasma samples as used in discovery. These data will be analyzed with a
multivariate longitudinal change-point model to form a multiple marker longitudinal algorithm for ED. This
classifier will be locked down. The classifier will be validated by assaying the custom panel of 20 ED
biomarkers on an independent PLCO serial plasma sample set, from cases (n=50) and 10:1 matched controls
(n=500). From these data the classifier will be assessed for two dimensions of sensitivity for early detection: (i)
the number of months prior to detection in PLCO, and (ii) proportion of cases detected, while (iii) maintaining a
high specificity goal of 98% - or a false positive rate of 2%. This low false positive rate requires a large number
of controls (n=500) for its accurate assessment.
项目总结
项目成果
期刊论文数量(0)
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会议论文数量(0)
专利数量(0)
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Steven J Skates其他文献
Importance of tumor size and repopulation for radiocurability of skin cancer.
肿瘤大小和增殖对于皮肤癌放射治疗的重要性。
- DOI:
- 发表时间:
1993 - 期刊:
- 影响因子:0
- 作者:
Maciejewski Ba;Steven J Skates;A. Zajusz;D. Lange - 通讯作者:
D. Lange
Steven J Skates的其他文献
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{{ truncateString('Steven J Skates', 18)}}的其他基金
Novel Serum, Plasma, and Urine Biomarkers of Ovarian Can
卵巢癌的新型血清、血浆和尿液生物标志物
- 批准号:
6991022 - 财政年份:2004
- 资助金额:
$ 12万 - 项目类别:
MEASURING AND STATISTICAL MODELING OF SERIAL PSA LEVELS
系列 PSA 水平的测量和统计建模
- 批准号:
2733338 - 财政年份:1997
- 资助金额:
$ 12万 - 项目类别:
OPTIMAL SCREENING FOR PROSTATE CA WITH SERIAL PSA LEVELS
通过连续 PSA 水平对前列腺 CA 进行最佳筛查
- 批准号:
2552697 - 财政年份:1997
- 资助金额:
$ 12万 - 项目类别:
OPTIMAL SCREENING FOR PROSTATE CA WITH SERIAL PSA LEVELS
通过连续 PSA 水平对前列腺 CA 进行最佳筛查
- 批准号:
2796352 - 财政年份:1997
- 资助金额:
$ 12万 - 项目类别:
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