Abstract 1163: Detection of hepatocellular carcinoma cases using a multiplex cancer biomarker panel.
Authors: Mathew Anu , Glezer Eli N. , Stengelin Martin , Wang Mingyue , Wohlstadter Jacob N. 
Published: August 2014

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide with a 5-year survival rate of only 14% in the United States. The age-adjusted incidence rate of HCC in the United States is high and rapidly rising (from 1.6 per 100,000 in 1975 to 7.9 in 2009). The only clinically useful serum biomarker for HCC is alpha-fetoprotein (AFP), which has a reported sensitivity of 39 to 64% and specificity of 76 to 91%. This is neither sensitive nor specific enough to be useful, especially since most HCC cases are detected at an advanced state when curative surgery is no longer possible.

In this study, the effectiveness of other cancer-related biomarkers in specifically detecting HCC was evaluated using an electrochemiluminescence-based, multiplex serum/plasma immunoassay panel developed on the MSD® platform. An MSD MULTI-ARRAY® 10-plex assay panel (AFP, carcino-embryonic antigen [CEA], cancer antigen 125 [CA125 or Muc-16], carbohydrate antigen 19-9 [CA19-9, sialyl Lewisa], osteopontin [OPN], matrix metalloproteinase 9 [MMP-9], ErbB2, E-cadherin, soluble epidermal growth factor receptor [EGFR], and cKit) was used to screen 25 HCC, 25 cirrhosis (alcohol-induced or due to fatty liver disease), and 30 normal subject serum samples. The assay protocol was simple: a small volume of sample was diluted and added to blocked and washed plates. After a 2-hour incubation with agitation, plates were washed and detection antibody reagent was added. After a 1-hour incubation, plates were washed and read on an MSD SECTOR® Imager 6000 (read time 70 seconds).

The levels of AFP, CEA, CA125, and CA19-9 were found to be significantly elevated in the HCC samples compared to levels in the cirrhosis and/or normal samples. The levels of OPN, MMP-9, E-cadherin, and ErbB2 were also significantly altered in the different sample types. Some of these biomarkers, either alone or in combination, were better than AFP alone at distinguishing HCC patients from controls. Combinations of these biomarkers could provide superior performance compared to existing HCC detection modalities. The selected biomarkers must be further evaluated using different sample cohorts to determine effectiveness for detection of HCC cases, particularly in those with different etiologies of development. Early detection of HCC in patients would enable therapeutic intervention at a stage where it would be most effective, significantly reducing mortality rates for HCC, one of the few cancers showing increasing incidence in the United States.

Citation Format: Anu Mathew, Eli N. Glezer, Martin Stengelin, Mingyue Wang, Jacob N. Wohlstadter. Detection of hepatocellular carcinoma cases using a multiplex cancer biomarker panel. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1163. doi:10.1158/1538-7445.AM2013-1163

Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.