= Emerging. More than 5 years before clinical availability. (26.62%)
= Expected to be clinically available in 1 to 4 years. (38.91%)
= Clinically available now. (34.47%)
MSACL 2020 US : Mehta

MSACL 2020 US Abstract

Topic: Imaging

Podium Presentation in Room 4 on Wednesday at 16:55 (Chair: Kevin Schey / Marissa Jones)

Imaging Mass Spectrometry Analysis of Glycans from Tissue to Serum - Identification and Validation of Biomarkers for Hepatocellular Carcinoma

Anand Mehta (Presenter)
Medical University of South Carolina

Presenter Bio(s): Anand Mehta, D.Phil., is the SmartState Endowed Chair in Proteomic Biomarkers and Professor, Department of Cell and Molecular Pharmacology at the Medical University of South Carolina. Dr. Mehta’s laboratory is focused on understanding and developing diagnostic methods and treatments for hepatocellular carcinoma (HCC). HCC is a primary cancer of the liver and kills close to 1 million people every year. The Mehta lab was one of the first to perform total serum glycan analysis for biomarker detection and one of the first to perform serum glycoproteomics. His laboratory remains on the forefront in the development of tools for the analysis of complex carbohydrates and the discovery and validation of biomarkers of HCC.

Authors: Anand S. Mehta (1), Mengjun Wang (1), Connor West (1), Richard R. Drake (1), Yujin Hoshida (2), and Amit Singal(2)
(1) Medical University of South Carolina, (2) The University of Texas Southwestern Medical Center.

Abstract

Goal: Identify serum glycoprotein biomarkers of hepatocellular carcinoma (HCC) that originate directly from cancer tissue.

Methods: Formalin-fixed human liver tissue from patients with healthy livers, cirrhotic livers, or HCC were evaluated using N-glycan MALDI imaging mass spectrometry on a Solarix dual source 7T MALDI-FTICR (Bruker Daltonics). A thin molecular coating of PNGase F was applied to the tissue using a TMSprayer (HTX Technologies LLC). Data was analyzed using FlexImaging and SCiLS Lab software (Bruker Daltonics). In total, 238 HCC tissue samples and 235 control tissue samples were analyzed. Subsequently, serum glycoproteomics was performed using a recombinant lectin with greater affinity toward branched and fucosylated glycan. Proteins identified as containing the same glycans observed in HCC tissue were further examined in five independent and blinded sample sets consisting of 695 patients, 321 with liver cirrhosis and 374 with HCC, including 288 with early stage HCC both at the time of sample collection and at a time point of up to 16 months prior to HCC detection.

Results: Through tissue-based glycan imaging, increased levels of fucosylation was observed in 96% of the HCC tissues examined. The glycan most often observed increased in HCC tissue was a tetra-antennary glycan with one to three fucose residues. Using a recombinant AAL lectin which has increased affinity towards fucosylated and branched glycan, we identified a number of serum proteins that contain tetra-antennary glycan with one to three fucose residues. Subsequently two assays were developed to exploit these findings. The first was a plate-based assay using high affinity antibodies to one of these proteins, low molecular weight kininogen (LMWK), and recombinant lectins with high affinity towards the specific fucose change observed was used to test the performance of fucosylated LMWK as a biomarker of HCC. In four independent studies, a fucosylated LMWK based biomarker algorithm had a median AUC of 0.9575 in the detection of all HCC, 0.945 for early stage HCC, and 0.916 for the detection of early stage HCC at a time point of 6 months prior to HCC detection. The second assay combined antibody microarrays to the identified proteins with high throughput glycan analysis of the captured proteins through glycan imaging and allowed for the creation of a glycan signature to identify early stage HCC.

Conclusions: Using a novel tissue-based glycan imaging mass spectrometry platform, we were able to identify glycan changes that occur directly in cancer tissue and used this information to identify serum-based biomarkers of HCC that are far superior to those currently used.


Financial Disclosure

DescriptionY/NSource
GrantsyesGlycotest, Inc
SalaryyesGlycotest, Inc
Board MemberyesGlycotest, Inc, N-Zyme LLC
Stockyes Glycotest, Inc, N-Zyme LLC
ExpensesyesGlycotest, Inc, N-Zyme LLC
IP RoyaltyyesGlycotest, Inc

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes