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Grant Details

Grant Number: 5R21CA238651-02 Interpret this number
Primary Investigator: Zhang, Xuehong
Organization: Brigham And Women'S Hospital
Project Title: Proteomics Study of Non-Viral Related Hepatocellular Carcinoma Risk
Fiscal Year: 2021


Abstract

Project Summary/Abstract In the United States, hepatocellular carcinoma has one of the most rapidly increasing incidence rates among both men and women. This sharp increase in incidence is coupled with a median survival of less than one year, as most liver cancer cases are diagnosed at late stages and are not eligible for curative therapy, while outcomes dramatically improve for asymptomatic, early stage localized hepatocellular carcinoma, with significant improved 5-year survival rates with surgical resection or liver transplantation. Furthermore, there is currently no effective surveillance strategy for early hepatocellular carcinoma detection in clinical practice. We therefore propose to identify new hepatocellular carcinoma-specific plasma protein biomarkers that can contribute to the detection of early stage hepatocellular carcinoma when cure is more likely. Although proteomics is an extremely useful and high-throughput analytical platform for hepatocellular carcinoma biomarker discovery, identifying biomarkers through proteomics-based approaches is limited due to the lack of a systematic proteome screen and its limited ability to accurately detect low-abundance proteins. SOMAscan, a novel highly multiplexed, high sensitivity aptamer-based immuno-like biomarker discovery technology, has been applied successfully for biomarker discovery in some other diseases. More recently, based on our preliminary data, we provide solid evidence as to the potential ability of SOMAscan to identify novel, low abundance, blood-based biomarkers in liver diseases with great accuracy. We will therefore apply SOMAscan to hepatocellular carcinoma by systematically measuring the expression level of 1,305 biologically relevant human plasma proteins, including low abundant cytokines across the whole dynamic range. We will further validate the candidate protein biomarkers in an independent study using ELISA. Upon completion of this proposed study we expect to have identified novel plasma protein biomarkers that could contribute to early detection of hepatocellular carcinoma and generate new insights into hepatocellular carcinoma pathogenesis. The integration of proteomics within the cohorts and the state-of-the-art proteomics platform has the potential to ultimately transform hepatocellular carcinoma detection and management, therefore reducing the mortality of this deadly disease.



Publications

Blood Magnesium Level and Risk of Hepatocellular Carcinoma in a Prospective Liver Cirrhosis Cohort.
Authors: Zhang X. , Zhao L. , Dai Q. , Hou T. , Danford C.J. , Lai M. , Zhang X. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2024-10-02 00:00:00.0; 33(10), p. 1368-1374.
PMID: 39037332
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Ultra-processed products and risk of liver cancer: A prospective cohort study.
Authors: Zhao L. , Zhang X. , Yu D. , Wang L. , Shrubsole M.J. , Zheng W. , Sudenga S.L. , Zhang X. .
Source: Clinical Nutrition (edinburgh, Scotland), 2024 Oct; 43(10), p. 2298-2304.
EPub date: 2024-08-17 00:00:00.0.
PMID: 39226717
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Diabetes risk reduction diet and risk of liver cancer and chronic liver disease mortality: A prospective cohort study.
Authors: Chen Y. , Zhao L. , Jung S.Y. , Pichardo M.S. , Lopez-Pentecost M. , Rohan T.E. , Saquib N. , Sun Y. , Tabung F.K. , Zheng T. , et al. .
Source: Journal Of Internal Medicine, 2024-09-06 00:00:00.0; , .
EPub date: 2024-09-06 00:00:00.0.
PMID: 39239793
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Pre-diagnostic plasma inflammatory proteins and risk of hepatocellular carcinoma in three population-based cohort studies from the United States and the United Kingdom.
Authors: Zhao L. , Zhang X. , Birmann B.M. , Danford C.J. , Lai M. , Simon T.G. , Chan A.T. , Giovannucci E.L. , Ngo L. , Libermann T.A. , et al. .
Source: International Journal Of Cancer, 2024-06-11 00:00:00.0; , .
EPub date: 2024-06-11 00:00:00.0.
PMID: 38861327
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Pre-diagnostic plasma proteomics profile for hepatocellular carcinoma.
Authors: Zhang X. , Zhao L. , Ngo L.H. , Dillon S.T. , Gu X. , Lai M. , Simon T.G. , Chan A.T. , Giovannucci E.L. , Libermann T.A. , et al. .
Source: Journal Of The National Cancer Institute, 2024-05-01 00:00:00.0; , .
EPub date: 2024-05-01 00:00:00.0.
PMID: 38688524
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Association of dietary insulinemic and inflammatory potential with risk of liver cancer and chronic liver disease mortality in postmenopausal women: a prospective cohort study.
Authors: Zhang X. , Zhao L. , Christopher C.N. , Tabung F.K. , Bao W. , Garcia D.O. , Shadyab A.H. , Saquib N. , Neuhouser M.L. , Tinker L.F. , et al. .
Source: The American Journal Of Clinical Nutrition, 2023 Sep; 118(3), p. 530-537.
EPub date: 2023-07-17 00:00:00.0.
PMID: 37460062
Related Citations

Higher ultra-processed food intake was positively associated with odds of NAFLD in both US adolescents and adults: A national survey.
Authors: Zhao L. , Zhang X. , Martinez Steele E. , Lo C.H. , Zhang F.F. , Zhang X. .
Source: Hepatology Communications, 2023-09-01 00:00:00.0; 7(9), .
EPub date: 2023-08-31 00:00:00.0.
PMID: 37655983
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Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality.
Authors: Zhao L. , Zhang X. , Coday M. , Garcia D.O. , Li X. , Mossavar-Rahmani Y. , Naughton M.J. , Lopez-Pentecost M. , Saquib N. , Shadyab A.H. , et al. .
Source: Jama, 2023-08-08 00:00:00.0; 330(6), p. 537-546.
PMID: 37552302
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Gallstones and risk of cancers of the liver, biliary tract and pancreas: a prospective study within two U.S. cohorts.
Authors: Luo X. , Yang W. , Joshi A.D. , Wu K. , Simon T.G. , Yuan C. , Jin L. , Long L. , Kim M.N. , Lo C.H. , et al. .
Source: British Journal Of Cancer, 2022-06-17 00:00:00.0; , .
EPub date: 2022-06-17 00:00:00.0.
PMID: 35715632
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Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality.
Authors: Liu X. , Yang W. , Petrick J.L. , Liao L.M. , Wang W. , He N. , Campbell P.T. , Zhang Z.F. , Giovannucci E. , McGlynn K.A. , et al. .
Source: Nature Communications, 2021-11-04 00:00:00.0; 12(1), p. 6388.
EPub date: 2021-11-04 00:00:00.0.
PMID: 34737258
Related Citations

Adiposity, Adulthood Weight Change and Risk of Incident Hepatocellular Carcinoma.
Authors: Simon T.G. , Kim M.N. , Luo X. , Liu X. , Yang W. , Ma Y. , Chong D.Q. , Fuchs C.S. , Stampfer M.J. , Giovannucci E.L. , et al. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2021-07-15 00:00:00.0; , .
EPub date: 2021-07-15 00:00:00.0.
PMID: 34266856
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Discovery and features of an alkylating signature in colorectal cancer.
Authors: Gurjao C. , Zhong R. , Haruki K. , Li Y.Y. , Spurr L.F. , Lee-Six H. , Reardon B. , Ugai T. , Zhang X. , Cherniack A.D. , et al. .
Source: Cancer Discovery, 2021-06-17 00:00:00.0; , .
EPub date: 2021-06-17 00:00:00.0.
PMID: 34140290
Related Citations

Association of bowel movement frequency and laxative use with risk of hepatocellular carcinoma in US women and men.
Authors: Long L. , Liu X. , Jin L. , Simon T. , Ma W. , Kim M.N. , Yang W. , Meyerhardt J.A. , Chan A.T. , Giovannucci E. , et al. .
Source: International Journal Of Cancer, 2021-05-24 00:00:00.0; , .
EPub date: 2021-05-24 00:00:00.0.
PMID: 34028016
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Incident Type 2 Diabetes Duration and Cancer Risk: A Prospective Study in Two US Cohorts.
Authors: Hu Y. , Zhang X. , Ma Y. , Yuan C. , Wang M. , Wu K. , Tabung F.K. , Tobias D. , Hu F.B. , Giovannucci E. , et al. .
Source: Journal Of The National Cancer Institute, 2021-04-06 00:00:00.0; 113(4), p. 381-389.
PMID: 33225344
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Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma.
Authors: Yang W. , Sui J. , Zhao L. , Ma Y. , Tabung F.K. , Simon T.G. , Lee D.H. , Zeng X. , Nguyen L.H. , Meyerhardt J.A. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2021-01-29 00:00:00.0; , .
EPub date: 2021-01-29 00:00:00.0.
PMID: 33514605
Related Citations

Plant-Based and Animal-Based Low-Carbohydrate Diets and Risk of Hepatocellular Carcinoma Among US Men and Women.
Authors: Liu Y. , Yang W. , VoPham T. , Ma Y. , Simon T.G. , Gao X. , Chan A.T. , Meyerhardt J.A. , Giovannucci E.L. , Zhang X. .
Source: Hepatology (baltimore, Md.), 2021 Jan; 73(1), p. 175-185.
PMID: 32222996
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Dietary intake of branched-chain amino acids and survival after colorectal cancer diagnosis.
Authors: Long L. , Yang W. , Liu L. , Tobias D.K. , Katagiri R. , Wu K. , Jin L. , Zhang F.F. , Luo X. , Liu X. , et al. .
Source: International Journal Of Cancer, 2020-12-19 00:00:00.0; , .
EPub date: 2020-12-19 00:00:00.0.
PMID: 33341092
Related Citations

Comments on "One-carbon metabolism-related micronutrients intake and risk for hepatocellular carcinoma: A prospective cohort study".
Authors: Zhao L. , Zhang X. .
Source: International Journal Of Cancer, 2020-07-04 00:00:00.0; , .
EPub date: 2020-07-04 00:00:00.0.
PMID: 32621756
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Association between yogurt consumption and plasma soluble CD14 in two prospective cohorts of US adults.
Authors: Luo X. , Sui J. , Birmann B.M. , Ivey K.L. , Tabung F.K. , Wu Y. , Yang W. , Wu K. , Ogino S. , Liu H. , et al. .
Source: European Journal Of Nutrition, 2020-06-16 00:00:00.0; , .
EPub date: 2020-06-16 00:00:00.0.
PMID: 32548645
Related Citations

Physical activity and risk of hepatocellular carcinoma among U.S. men and women.
Authors: Luo X. , Yang W. , Ma Y. , Simon T.G. , Meyerhardt J.A. , Chan A.T. , Giovannucci E.L. , Zhang X. .
Source: Cancer Prevention Research (philadelphia, Pa.), 2020-04-20 00:00:00.0; , .
EPub date: 2020-04-20 00:00:00.0.
PMID: 32312712
Related Citations

High Dietary Intake of Vegetable or Polyunsaturated Fats is Associated With Reduced Risk of Hepatocellular Carcinoma.
Authors: Yang W. , Sui J. , Ma Y. , Simon T.G. , Petrick J.L. , Lai M. , McGlynn K.A. , Campbell P.T. , Giovannucci E.L. , Chan A.T. , et al. .
Source: Clinical Gastroenterology And Hepatology : The Official Clinical Practice Journal Of The American Gastroenterological Association, 2020-01-09 00:00:00.0; , .
EPub date: 2020-01-09 00:00:00.0.
PMID: 31927110
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