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.
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