Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
基本信息
- 批准号:9893835
- 负责人:
- 金额:$ 61.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-03-14 至 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:Annual ReportsAntibodiesBiological MarkersBloodCellsChoristomaChronicCirrhosisClinical DataCommunitiesDetectionDevelopmentDiagnosticEarly DiagnosisEtiologyFamilyFucoseGalactoseGeneticGenetic HeterogeneityGlycoproteinsGrantHepatitis BHepatitis C virusHeterogeneityImageKininogensLaboratoriesLectinLinkLiverLiver CirrhosisLiver FibrosisLiver diseasesMalignant NeoplasmsMalignant neoplasm of liverMalignant neoplasm of pancreasMethodsModificationMutationObesityPatientsPatternPerformancePolysaccharidesPositioning AttributePrimary carcinoma of the liver cellsProteinsProteomicsSamplingScreening for cancerSerumSialic AcidsSourceSpecificitySpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationStructureTestingTissue SampleTissuesUnited StatesValidationVirus DiseasesWomanalpha-Fetoproteinsarmbasebiomarker panelcancer biomarkerscancer geneticscancer heterogeneitycancer preventioncancer subtypesdiagnostic panelearly detection biomarkersfallsgenetic profilingglycoproteomicsglycosylationimprovedinterestmenmortalitynon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnovelnovel markersugartumortumor heterogeneity
项目摘要
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.
文摘:
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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RICHARD R. DRAKE其他文献
RICHARD R. DRAKE的其他文献
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{{ truncateString('RICHARD R. DRAKE', 18)}}的其他基金
Targeted Isolation and Identification of Sialylated Glycoproteins in Cancer Tissues, Cells and Biofluids
癌症组织、细胞和生物液中唾液酸化糖蛋白的靶向分离和鉴定
- 批准号:
10358217 - 财政年份:2022
- 资助金额:
$ 61.56万 - 项目类别:
Targeted Isolation and Identification of Sialylated Glycoproteins in Cancer Tissues, Cells and Biofluids
癌症组织、细胞和生物液中唾液酸化糖蛋白的靶向分离和鉴定
- 批准号:
10592315 - 财政年份:2022
- 资助金额:
$ 61.56万 - 项目类别:
Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
- 批准号:
10576851 - 财政年份:2019
- 资助金额:
$ 61.56万 - 项目类别:
Glycopathology of HCC: identification of the source cells of serum fucosylation
HCC 糖病理学:血清岩藻糖基化来源细胞的鉴定
- 批准号:
10361210 - 财政年份:2019
- 资助金额:
$ 61.56万 - 项目类别:
Detection and Histopathology Localization of O-Glycans and Glycosaminoglycans in Tissues
组织中 O-聚糖和糖胺聚糖的检测和组织病理学定位
- 批准号:
9320983 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
Detection and Histopathology Localization of O-Glycans and Glycosaminoglycans in Tissues
组织中 O-聚糖和糖胺聚糖的检测和组织病理学定位
- 批准号:
9166181 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors
定义具有免疫和肿瘤微环境因素的综合稳态负荷指数
- 批准号:
9145866 - 财政年份:2016
- 资助金额:
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Defining an Integrated Allostatic Load Index with Immune and Tumor Microenvironment Factors
定义具有免疫和肿瘤微环境因素的综合稳态负荷指数
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10562431 - 财政年份:2016
- 资助金额:
$ 61.56万 - 项目类别:
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