Project Details
Abstract
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
External Project ID:NSC101-2325-B182-011
Status | Finished |
---|---|
Effective start/end date | 01/05/12 → 30/04/13 |
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