PROVIDED. The incidence of HCV-associated hepatocellular carcinoma (HCC) is rising in the United States and Europe and is likely to double or triple over the next 10 to 20 years. The overall survival rate of HCC is poor because most patients are diagnosed when the tumor is in an advanced stage. Our group has embarked on an effort to integrate genomics, transcriptomics and proteomics for the profiling of HCC. We have also utilized a proteomic approach to determine whether a distinct repertoire of autoantibodies can be detected in the sera of HCC patients and identified a diverse set of tumor antigens that induce a humoral response during the development of HCC. Our integrated DNA/RNAIProteinlAntigen approach has provided new insights into genes that are potentially important in HCC development, as well as a potential for identifying new markers for early HCC diagnosis. Our approach also provided evidence for an association between the etiology of the underlying liver disease and patterns of HCC development. We propose to integrate genomic and proteomic approaches to identify genes and proteins that are expressed distinctively between HCV-related HCCs and precursor lesions. The combination of genomic and proteomic based profiling uniquely allows delineation of global changes in expression patterns resulting from transcriptional and post-transcriptional control, post- translational modifications and shifts in proteins between cellular compartments. It will allow the identification of changes in gone expression associated with the development of HCC, some of which may correlate with the appearance of the tumor. Testing and validation of these potential markers require high affinity probes for their detection and quantitation. For this purpose, we propose to acquire corresponding antibodies and to develop antibody-based microarrays to determine their level in sera and their utility for diagnosing HCC. The use of microarrays to this effect provides a high throughput high sensitivity and low serum volume requirement and therefore is highly advantageous. We will establish the sensitivity and specificity of the individual and combination of protein biomarkers. The identification of panels of tumor antigens that elicit a humoral response may also have utility in cancer screening and diagnosis. We propose to identify circulating antibodies to tumor antigens that will enable us to develop a blood test for HCC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK066840-05S2
Application #
7994250
Study Section
Special Emphasis Panel (ZRG1-GMA-2 (50))
Program Officer
Doo, Edward
Project Start
2010-01-15
Project End
2010-12-31
Budget Start
2010-01-15
Budget End
2010-12-31
Support Year
5
Fiscal Year
2010
Total Cost
$100,000
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
078200995
City
Seattle
State
WA
Country
United States
Zip Code
98109
da Costa, Andre Nogueira; Plymoth, Amelie; Santos-Silva, Daniela et al. (2015) Osteopontin and latent-TGF ? binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma. Int J Cancer 136:172-81
Shang, Sufen; Plymoth, Amelie; Ge, Shaokui et al. (2012) Identification of osteopontin as a novel marker for early hepatocellular carcinoma. Hepatology 55:483-90
Lai, Keane K Y; Shang, Sufen; Lohia, Neha et al. (2011) Extracellular matrix dynamics in hepatocarcinogenesis: a comparative proteomics study of PDGFC transgenic and Pten null mouse models. PLoS Genet 7:e1002147
Cermelli, Silvia; Ruggieri, Anna; Marrero, Jorge A et al. (2011) Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic fatty liver disease. PLoS One 6:e23937
Liu, Yashu; He, Jintang; Li, Chen et al. (2010) Identification and confirmation of biomarkers using an integrated platform for quantitative analysis of glycoproteins and their glycosylations. J Proteome Res 9:798-805
Beretta, Laura (2010) Liver proteomics applied to translational research in liver disease and cancer. Proteomics Clin Appl 4:359-61
Beretta, Laura (2010) HUPO's effort to define the liver proteome. J Proteome Res 9:637-8
Lee, Nikki P; Chen, Lei; Lin, Marie C et al. (2009) Proteomic expression signature distinguishes cancerous and nonmalignant tissues in hepatocellular carcinoma. J Proteome Res 8:1293-303
Parent, Romain; Qu, Xiaoyu; Petit, Marie-Anne et al. (2009) The heat shock cognate protein 70 is associated with hepatitis C virus particles and modulates virus infectivity. Hepatology 49:1798-809
Beretta, Laura (2009) Comparative analysis of the liver and plasma proteomes as a novel and powerful strategy for hepatocellular carcinoma biomarker discovery. Cancer Lett 286:134-9

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