Abstract 2358: Serum biomarkers Carcinoembryonic Antigen (CEA) and Human Aspartyl (Asparaginyl) Beta Hydroxylase (HAAH) compared in normal volunteers, smokers, and stage I/II lung cancer patients.
Authors: Semenuk Mark A. , Ghanbari Hossein A. 
Published: August 2014

Serological biomarkers for detection of cancer are often based upon measuring the ectopic expression of particular proteins that are otherwise only expressed during embryonic development. Perhaps the oldest and best known cancer biomarker in this class is carcinoembryonic antigen (CEA), which despite having some limitations, has been very popular in its longstanding use. We have compared CEA with HAAH (Human Aspartyl (Asparaginyl) beta hydroxylase), an emerging biomarker protein that like CEA has an onco-developmental re-expression pattern in a number of cancers including lung cancer.

One of the limitations of CEA that precludes its routine utility for early serological screening and detection of lung cancer is that cigarette smokers, a lung cancer high risk group, frequently have elevated and variable CEA levels compared to normal non-smoking individuals. We compared serum CEA by ELISA (using a commercial kit) with serum HAAH (using Panacea's technology) in 26 individuals each who were either normal, cigarette smokers, or a population of patients with either stage I or II lung cancer. Both assays used a double monoclonal antibody sandwich format, and a peroxidase /TMB detection system with suitable calibration standards . The CEA assay had a simultaneous format, differing from the HAAH ELISA which had a sequential homolgous antibody format.

The mean CEA level of smokers (2.7 ng/ mL, range 0.84-6.4) was double that of normal (1.3 ng/ mL range 0.77- 2.4) as expected. Several individuals clustered near or exceeded the cut off of 5ng /mL. More striking was the significant overlap of CEA levels between smokers and the lung cancer patients (&gt;80 %) (whereas &gt; 53% overlap between normals and lung cancer). It is even more striking to observe a 100% overlap between smokers and stage I lung cancer. It's interesting that a similar pattern of HAAH expression was seen between normals and smokers (two times higher). However, both of these groups mostly clustered below a pre-established cutoff of 2 ng/ mL and were scored negative and non-detectable by our acceptance parameters. Comparison of HAAH levels between normals/smokers and lung cancer patients clearly shows a distinction between these groups with 0 % overlap between normals/smokers and cancer patients.

The concept of ELISA based serological screening for lung cancer is generally very well received as a cost effective non-invasive potential means for detection. Our early assessment of HAAH levels in smokers indicates that such testing performs favorably when compared to CEA testing in the effective detection of early stage lung cancer. Since cigarette smokers contribute to an overall 87% association with lung cancer, it's more likely that these individuals would be selected for voluntary screening and would therefore benefit from the superior performance of the HAAH ELISA.

Citation Format: Mark A. Semenuk, Hossein A. Ghanbari. Serum biomarkers Carcinoembryonic Antigen (CEA) and Human Aspartyl (Asparaginyl) Beta Hydroxylase (HAAH) compared in normal volunteers, smokers, and stage I/II lung cancer patients. [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 2358. doi:10.1158/1538-7445.AM2013-2358