(101CAP1003-1) Development of a Proteomics---Based Pipeline for Verification of Targeted Cancer Biomarkers in Body Fluids (I)

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details


Cancer is one of the main causes of human death worldwide. The majority of cancers are initially diagnosed in their advanced stages, representing one of the reasons for the high mortality rate of cancer. Non-invasive, body fluid-accessible biomarkers represent attractive targets for the strategy development of early cancer detection. However, currently used biomarkers for cancer detection in clinics are lack of sensitivity and specificity sufficient for this purpose. Although a lot of candidate cancer biomarkers have been discovered in the past decade, very few of them have been verified (in 100-1000s samples) and validated (in >1000s samples) in parallel to check and compare their clinical utilities, which represents one of the bottle-neck steps for successful cancer biomarker development. To tackle this problem, we have organized three component projects in the present program project entitled “Application of high-throughput, multiplexed technology platforms for verification of targeted cancer biomarkers in body fluids”. At first, three technology platforms targeting on proteins, miRNAs and autoantibodies will be developed, respectively. Regarding protein targets, a technology platform using mass spectrometry (MS)-based Multiple Reaction Monitoring (MRM) measurements in conjunction with peptide enrichment in plasma using anti-peptide antibodies (the “immuno-MRM” platform) has been recently reported to successfully quantify dozens of targeted proteins in single assay with acceptable precision and sensitivity. As this immuno-MRM platform represents a feasible approach for multiplexed protein quantification and we have already established the MRM-based technology for multiplexed quantification of >60 proteins in human body fluids (Chen et al., J. Proteomics in press), we plan to further develop the immuno-MRM-based pipeline for verification of targeted protein biomarkers in body fluids in this component project. Oral squamous cell carcinoma (OSCC) is selected as the first testing model for the development of this technology platform because it has become a growing burden of health care system of Taiwan and there are no any biomarkers for aiding the early detection and management of this disease. The specific aims of this component project are: (1) To produce and characterize monoclonal anti-peptide antibodies for 50 target proteins prioritized from ~250 candidate OSCC biomarkers collected from >500 literatures and our in-house database. (2) To develop and optimize the immuno-MRM assays in plasma and saliva samples from OSCC-related patients using the successfully produced monoclonal anti-peptide antibodies and a QTRAP5500 LC-MRM/MS system. (3) Using the developed immuno-MRM assays to simultaneously quantify the 50 target proteins in saliva and plasma specimens from different subject groups to identify good biomarker panel(s) for discriminating early OSCC from both healthy controls and patients harboring precancerous lesions. (4) To combine the protein biomarker panels with miRNA and autoantibody biomarkers identified in the other two component projects for improving efficacy in early OSCC detection. Form this component project, we expect to create the first immuno-MRM-based pipeline for verification of candidate OSCC biomarkers and to identify OSCC biomarker panels that are deserved for further validation in a large sample cohort collected from multi-centers. If this pipeline is successful, it could also be applied to other cancer types or diseases for verification of useful body fluid-accessible protein biomarkers in the near future.

Project IDs

Project ID:PC10106-0037
External Project ID:NSC101-2325-B182-011
Effective start/end date01/05/1230/04/13


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