# Serum Glyco-Markers of Early Hepatocellular Carcinoma Using a Mass Spec Approach

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $360,861

## Abstract

Abstract: Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death
worldwide. Most cases of HCC develop in patients that already have liver cirrhosis and have been
recommended for surveillance for an early onset of HCC. Only 20-30% of patients with HCC are
currently eligible for curative therapy with surgical resection where the impact of these therapeutic
interventions on the overall survival of patients with HCC is related to the detection of HCC at earlier
stages. With the development of new markers one would hope to increase the proportion of patients
that can be offered curative therapies and significantly impact the survival of patients with this disease.
In our previous work we have found several glycoprotein markers of early stage HCC versus cirrhosis
which can provide a performance that is potentially better than that of AFP or together with AFP can
improve its overall performance. In particular a bifucosylated glycan structure found in haptoglobin from
HCC patients is undergoing a phase 2 EDRN blinded validation where this marker appears to improve
the performance for detection of early stage HCC of all etiologies. A new strategy that has been
investigated is to screen serum for large numbers of core-fucosylated(CF) sites using mass
spectrometry where over 1300 sites have been detected in the serum of HCC patients. We have found
several CF-glycopeptides in serum that can distinguish between early HCC and cirrhosis and which are
etiology specific for HCV-HCC versus HCV-cirrhosis and ALC-HCC versus ALC-cirrhosis. In the work
proposed herein, we will develop a mass spec based assay that is specific for detecting candidate CF-
glycopeptides that are differentially expressed in serum of early HCC patients versus cirrhosis. It
involves digestion of proteins in total serum to glycopeptides followed by enzymatic removal of the
glycan down to the GlcNAc-Fuc core fucosylation. The CF-glycopeptides are labeled with isotopic tags
and analyzed by a novel glyco-MRM(multiple reaction monitoring) assay using tandem mass
spectrometry where differences in CF expression between HCC and cirrhosis can be detected. This
method can be multiplexed for many markers simultaneously, does not require the use of antibodies
and can be automated. The hypothesis here is that these structural changes depend on a different
mechanism than protein level assays and could provide complementary information to the ELISA assay
for AFP where together they may provide an improved AUC. We will test these markers in a
confirmation set of 300 samples and evaluate their performance together with the ELISA assay for AFP
and a mass spec assay for bifucosylated Hp. The markers that are found to improve on the
performance of AFP either alone or in combination with AFP or the bifucosylated Hp assay will then
undergo a blinded validation in the phase 2 EDRN validation set. Markers that perform successfully in
this blinded validation will then go on for possibl...

## Key facts

- **NIH application ID:** 9959332
- **Project number:** 5R01CA160254-09
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** David M. Lubman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $360,861
- **Award type:** 5
- **Project period:** 2012-05-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959332

## Citation

> US National Institutes of Health, RePORTER application 9959332, Serum Glyco-Markers of Early Hepatocellular Carcinoma Using a Mass Spec Approach (5R01CA160254-09). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9959332. Licensed CC0.

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