AABH (aspartyl (asparaginyl) β-hydroxylase ) as a serum biomarker for colorectal cancer diagnosis and prognosis.

Abstract

22 Background: Colorectal cancer (CRC) is the third most common type of cancer diagnosed in the US. The National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) recommend that men and women begin colorectal cancer screening at age 50 or younger if they are at high risk. One of the following screening procedures is recommended: tests for fecal blood annually, a colonoscopy every 5 years, fecal occult blood tests in conjunction with colonoscopy every 5 years, a double-contrast barium enema every 5 years or a colonoscopy every 10 years. Fecal blood tests and colonoscopy are preferred over either test alone. Despite these recommendations, according to The Surveillance, Epidemiology and End Results Data Base (SEER), only 41% of colon cancers are diagnosed when the cancer is still confined to its primary site, 36% are diagnosed when the tumor has spread directly from its primary site or to regional lymph nodes, 19% are diagnosed when the cancer has already metastasized (4% unknown). The corresponding 5-year relative survival rates are 89.8% for localized disease, 67.7% for regional disease, and 10.3% for metastatic disease. Methods: Neither the NCCN nor the ACS recommends that a blood test be done as part of screening. This is due to the fact that, until now, there has not been a blood test with adequate sensitivity or specificity for this purpose. We have investigated the utility of aspartyl (asparaginyl) β-hydroxylase (AABH) as a screening test for colorectal cancer. Results: AABH has been detected by immunohistochemical staining (IHC) on the cell surface of a broad range of cancers including CRC. It has been detected by IHC in > 99% of tumor specimens tested (n > 2300) but has not been found in adjacent normal tissue and in tissue samples from people who do not have cancer. This observation and the observation that AABH is found in the serum of patients with cancer, but not in the serum of people who are cancer-free, led the development of a sandwich ELISA to measure AABH in serum. In the current study we have utilized the serum assay to quantify AABH levels in patients diagnosed with CRC and compared these values with those of people who did not have a diagnosis of cancer. Increased levels of AABH were found in the serum of 99% of patients with CRC (n = 175). In individuals not known to have cancer, AABH was essentially undetectable in serum (n = 213, specificity = 96%). Conclusions: AABH was identified in serum from patients with CRC irrespective of stage. Serum AABH levels for stages I, II, III and IV (local, regional, advanced regional and metastatic) were higher than 0.30 ng/mL (Cut off level). Thus, our data indicate that by measuring AABH in the serum, we should be able to detect colorectal cancer in most individuals at an earlier stage than it is currently detected. Hence, we believe that the broad application of this test could result in a much better 5-year survival for the majority of patients with colorectal cancer.