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Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma
Hongbo Sun1, Mei-Sze Chua, Dorothy Yang
1Asian Liver Center, Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305.
Insights
Researchers identified new protein markers to improve the diagnosis of hepatocellular carcinoma (HCC), a leading cause of cancer death. These novel biomarkers, detected using an antibody array, show promise in complementing existing tests like alpha-fetoprotein (AFP) for earlier detection.
Area of Science:
- Oncology
- Biomarker Discovery
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) is a major global cause of cancer mortality.
- Current diagnostic methods, primarily alpha-fetoprotein (AFP), lack sufficient sensitivity and specificity, leading to missed diagnoses in 30-50% of cases.
- Effective HCC treatment relies on early and accurate detection, necessitating the identification of novel diagnostic markers.
Purpose of the Study:
- To discover novel protein biomarkers for hepatocellular carcinoma (HCC) detection.
- To identify markers that can be used alone or in conjunction with alpha-fetoprotein (AFP).
- To evaluate potential diagnostic markers in plasma samples from HCC patients and those with viral hepatitis.
Main Methods:
- Utilized an antibody array platform to screen plasma samples from HCC patients and viral hepatitis patients.
- Identified proteins showing significant differential expression between HCC and hepatitis groups.
- Validated findings using independent immunoassay methods on separate patient cohorts.
Main Results:
- Identified 7 proteins (including AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, VCAM1) differentiating HCC from hepatitis patients.
- Discovered 8 additional proteins (including IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, SELL) that distinguish HCC patients with low AFP levels from hepatitis patients.
- Validated elevated plasma levels of CTNNB in HCC patients compared to hepatitis patients via immunoassay (p = 0.020).
Conclusions:
- An antibody array platform successfully identified potential circulating diagnostic markers for HCC.
- Several identified proteins show promise as complementary markers to AFP for improving HCC diagnosis.
- Further systematic evaluation is required to determine the clinical utility of these novel HCC diagnostic markers.
Abstract:
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP), the currently used HCC marker, misses 30%-50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48) and patients with chronic hepatitis B or C viral infections (n = 19) (both of which are the major risk factors of HCC). We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05) (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1). Importantly, we also identified 8 proteins that significantly differentiate HCC patients with 'normal' levels of AFP (< 20 ng/ml) from hepatitis patients (p < 0.05) (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL). These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020). In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.
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