Multiplexed Detection of Circulating Breast Tumor Antigen and Epigenetic Markers using Plasmon-enhanced Raman Spectroscopic Assay

Case ID:
C13581
Disclosure Date:
4/24/2015
Description:
Unmet Need
Breast cancer is the second leading cause of cancer-related mortality with an estimated 40,610 deaths for women in 2017. In the United States, the average chance of a women developing breast cancer is 1 in 8 and early breast cancer screening and detection is key in the treatment.
One method of early diagnosis is through surface–enhanced Raman spectroscopy (SERS). Raman spectroscopy can detect changes in molecular structure and composition, such as carbohydrate, lipids, proteins, and nucleic acids changes during early tumor diagnosis. Using SERS, indicators of breast cancer progression, such as circulating biomarkers and epigenetic biomarkers, can be identified. However, single markers are inadequate in describing the pathologic transformations and SERS sensing properties degrade rapidly. This technology utilizes SERS for early diagnostic methods for detecting multiple biomarkers in breast cancer.  
 
 
Technology Overview
The SERS platform offers a method of detecting breast tumor antigens and epigenetic markers (hypermethylated genes in circulating tumor DNA). The multiplexed detection of breast tumor antigens identifies cancer antigen (CA) 15-3, CA 27-29, cancer embryonic antigen (CEA), and epigenetic biomarkers that focus on 10 hypermethylated genes in tumor DNA. This technology uses gold (Au) nanostar-based SERS reporter and full-chip SERS spectroscopic imaging to provide a more reliable technique to determine aberrantly methylated genes and biomarker concentrations. Through these techniques, there is a higher sensitivity in detection than conventional immunoassays for breast cancer diagnosis and response monitoring. This technology uses SERS for non-invasive multiplexed detection of biomarkers and to improve sensitivity.
 
 
Stage of Development
The inventors’ previous studies in breast tumors and normal breast tissues have shown the utility of methylated biomarkers, such as statistically significant difference between methylation levels and ER/PR status, tumor relapse, and lymph node metastasis. A recent whole genome analysis of breast tissue DNA and circulating serum DNA yielded a 10-gene marker panel, which was verified in silico for sensitivity (90.9%), specificity (100%), and accuracy (95%). The Berman Lab recently demonstrated that nanoparticle-enhanced Raman assays are superior to conventional immunoassays (ELISA) in detecting CA 15-3, CA 27-29, and CEA. Ongoing studies will evaluate the assay performance in spiked sera and clinical specimens from breast cancer patients.
 
 
Publications
Chem Sci. 2015 Jul 1; 6(7): 3906-3914
Chem. Sci., 2016, 7, 6779-6785
Eng. J. Med. 2013, 368, 1199-209
Cancer Res. 2013, 73, 3206-3215
Proc. Nat. Acad. Sci. USA. 2013, 110, 471–476
Cancer Res. 2011, 71, 6195-6207
Cancer Res.  2014, 74, 2160-2170
PLoS ONE 2014, 9, e91805
 
Patent Information:
Inventors:
Category(s):
For Information, Contact:
Christine Joseph
cjoseph6@jhmi.edu
410-614-0300
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