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Glycopathology of HCC: identification of the source cells of serum fucosylation

Award Number: U01CA226052
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/14/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2025

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Glycopathology of HCC: identification of the source cells of serum fucosylation - Abstract: In the Annual Report to the Nation on the Status of Cancer, mortality from Hepatocellular carcinoma (HCC) increased at an annual rate of 2.8% in men and 2.2% in women, making it the cancer with the greatest increase in mortality in the United States (USA) over the last 10 years. The occurrence of liver cancer is predicted to continue rising in the USA and will exceed 50,000 cases by 2021. The majority of HCC arises in the background of liver fibrosis and cirrhosis, usually associated with chronic viral infection (hepatitis B and hepatitis C virus) or nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) associated with obesity. Our laboratory has shown alterations in both core and outer-arm fucosylation in HCC. These glycan modifications have promise as biomarkers of cancer and are actively being commercialized by a number of groups (including us). We have a developed a diagnostic panel that is comprised of clinical data along with one additional novel biomarker, fucosylated kininogen, that dramatically improves upon the detection of HCC, and in particular, the identification of those with early stage HCC. In an effort to identify the source of fucosylated serum glycoprotein, we have developed a novel method for tissue-based glycan analysis. In an analysis of 145 HCC tissue and 112 adjacent control or cirrhotic tissue control samples, we have identified two major changes in the N-linked glycan family that are associated with HCC. The first change observed was increased levels of fucosylation, a modification also often observed in serum of patients with HCC. However, ~50% of the tissue samples analyzed had no increase in fucose. Often these tumors without increased fucosylation had increases in tetra-antennary glycan. We hypothesize that the genetic heterogeneity of the tumor might have an impact upon the glycan heterogeneity in the tissue and serum. Consequently, the glycans may not only be used as biomarkers for the early detection of cancer but offer information into the specific genetics of the cancer. In this application, we will link the glycomic changes observed in both tissue and serum with the underlying genetic changes. As we will have matching tissue and serum, we will be able to determine if our current biomarker panel is capable of identifying fucose negative HCC. Lastly, we will utilize several proteomic and glycomic methods to identify biomarkers for cancer without increased levels of fucosylation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$279,564 )
2025	2023	THE MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	5	6/12/2025	NON-COMPETING CONTINUATION	-$279,564
														Subtotal = -$279,564

Issue Date FY: 2023 ( Subtotal = $603,318 )
2023	2023	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	5	2/7/2023	NON-COMPETING CONTINUATION	$603,318
														Subtotal = $603,318

Issue Date FY: 2022 ( Subtotal = $603,318 )
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	002	4	4/28/2022	NON-COMPETING CONTINUATION	$49,249
2022	2022	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	001	4	2/18/2022	NON-COMPETING CONTINUATION	$554,069
2022	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	3	11/12/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $603,318

Issue Date FY: 2021 ( Subtotal = $413,676 )
2021	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	001	3	5/7/2021	NON-COMPETING CONTINUATION	$0
2021	2021	MEDICAL UNIVERSITY OF SOUTH CAROLINA THE	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	3	2/26/2021	NON-COMPETING CONTINUATION	$413,676
														Subtotal = $413,676

Issue Date FY: 2020 ( Subtotal = $615,632 )
2020	2020	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	2	2/20/2020	NON-COMPETING CONTINUATION	$615,632
														Subtotal = $615,632

Issue Date FY: 2019 ( Subtotal = $552,594 )
2019	2019	MEDICAL UNIVERSITY OF SOUTH CAROLINA	179 ASHLEY AVE	CHARLESTON	SC	29425	CHARLESTON	USA	Cancer Detection and Diagnosis Research	000	1	3/14/2019	NEW	$552,594
														Subtotal = $552,594

Grand Total All Awards = $2,508,974

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Glycopathology of HCC: identification of the source cells of serum fucosylation

Award Number: U01CA226052

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/14/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2025

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