Das nukleäre Matrix Protein CC2 — ein Serummarker zur Früherkennung von kolorektalen Karzinomen

Abstract

The early diagnosis of colorectal cancer is central for effective treatment, as prognosis is directly related to the stage of the disease. When colorectal cancer is diagnosed at an early, localized stage, five-years survival is 90 %, with regional lymph node metastases survival drops to 45–60 % and with distant metastases five-year survival is below 5 %. Development of tumor markers in the blood from patients, which can detect colorectal cancer at an early stage, should have a major impact in morbidity and mortality of this disease. The nuclear matrix is the structural scaffolding of the nucleus and specific nuclear matrix proteins (NMPs) have been identified as an oncological »fingerprint« for various cancer types. We have successfully utilized this approach to develop an immunoassay that detected bladder cancer early in a clinical trial with a sensitivity of 96.4 % and a specificity of 100 % [1]. Initial study, using a prostate cancer antigen (EPCA) in plasma based immunoassay; prostate cancer could be detected with a sensitivity of 94 % and a specificity of 100 % [2].

Previous studies at our laboratory identified four colon cancer specific nuclear matrix proteins termed CC2 to CC5 [3];[4]. The objective of the present study was to analyze the expression of one of these proteins CC2 in serum from various patient populations and to determine whether CC2 antibodies could be used in a clinically applicable serum-based immunoassay specifically to detect colorectal cancer in an early stage.

Using a CC2 based indirect ELISA, the protein was measured in the serum from 200 individuals, including patients with colon and rectal cancer, healthy individuals, patients with diverticulosis, with colon polyps, with inflammatory bowel disease (IBD) and other gastrointestinal cancer patients. With a predetermined cutoff value of 0,6 OD we have successfully utilized this approach to develop an immunoassay that detected colorectal cancer in an early tumor stage in serum from patients with a sensitivity of 83,8 % (26/31) and a overall specificity of 87,5 %.

The results of this study has to be confirmed in larger clinical trials, but this initial study shows the potential of CC2 to serve as a highly specific blood based early detection marker for colorectal cancer.