Colon Cancer Secreted Protein 2 (CCSP-2) is a potential biomarker for colorectal cancer.

Abstract

LB-217

We report evidence that CCSP-2 is a serum biomarker of colon cancer, that it can be detected in the blood of human patients with disease, and may be of value in improving detecton of early disease recurrences in colon cancer patients. Colon cancer is the second leading cause of cancer death in the United States. However, the disease is eminently curable when detected early. Additionally, some individuals are cured or enjoy longterm survival when disease recurrences are detected early enough to be surgically treated. We previously reported CCSP-2 as a transcript that was up-regulated 70-fold in colon cancer and that was predicted to encode a secreted protein. We also showed that cancer cells secreted recombinant CCSP-2 into the blood in animal models, suggesting CCSP-2 as a potential serum biomarker for detection of colon cancer in humans. To investigate this possibility, we used recombinant CCSP-2 as an antigen for generating a panel of anti-CCSP-2 monoclonal antibodies. Using these antibodies, we now demonstrate the detection of endogenous CCSP-2 protein that is markedly expressed by human colon cancers. Furthermore, using two independent CCSP-2 ELISA assays that we developed, we also detected presence of CCSP-2 in human serum and plasma. Approximately 25% of colon cancer patients demonstrated serum and plasma levels of CCSP-2 elevated above the normal range. However, 79% of patients (27 of 34) demonstrated at least a 20% reduction in CCSP-2 in blood samples drawn five days post-operatively as compared to samples drawn pre-operatively. Moreover, the percent reduction in post-operative versus pre-operative CCSP-2 exceeded that of CEA (measured in the same sample) in 58% of cases (18 of 31), with the two assays showing equivalent decreases in 13% (4 of 31) cases. While serum CEA is commonly used for monitoring for early colon cancer recurrence, CEA detects surgically resectable disease in only 3-5% of patients who are so followed. Our data suggests that for many colon cancer patients, serum CCSP-2 provides a more sensitive marker of the presence of disease than does CEA. We suggest that serum CCSP-2 monitoring may, in many cases, provide a more sensitive method for detecting early and potentially curable colon cancer recurrences.