Abstract 2902: A simple blood test, evaluating the level of CD24 protein, can detect subjects with colorectal adenomas and adenocarcinomas

Abstract

Abstract Background: CD24 is a cell surface protein involved in cell adhesion and metastasis. Using gene expression array we have shown that CD24 expression is associated with colorectal cancer (CRC) [1,2]. The data was confirmed by IHC staining showing expression of CD24 in ∼90% of CR adenomas and adenocarcinomas. Two genetic variants of CD24, a C to T single nucleotide polymorphism (SNP), leading to an Ala/Val exchange (A57V) and a TG deletion in the 3’-UTR have been described, may have functional relevance, and affect CD24 protein level and stability. Objectives: To evaluate CD24 protein expression in peripheral blood leukocytes (PBLs) from normal, adenoma and CRC subjects, and score the associations of CD24 genetic variants and CRC risk. Methods: The calibration trial included 150 consented subjects (CRC=63, Adenomas=19, Normal=68) attending Tel Aviv Medical Center that underwent colonoscopy. PBLs were isolated and analyzed by Western blotting using anti-CD24. The samples were externally evaluated at the Technion, Haifa. The validation trial included 73 subjects. Additional 83 subjects were recently examined. Band intensities were scanned and tested for statistical significance. Sensitivity and specificity for CD24 was determined using receiver operating characteristic (ROC) curves. The study was approved by the Israel Ministry of Health. Results: The sensitivity and specificity of the CD24 test for distinguishing CRC from normal subjects was 70.5% (95% CI, 54.8-83.2%) and 83.8% (95% CI, 74.6-92.7%), respectively, and for advanced adenomas 84.2% (95% CI, 60.4-96.4%) and 73.5% (95% CI, 61.4-83.5%), respectively. The external evaluation study varied slightly. Improved values were achieved in the validation trial. Thus, the sensitivity for the detection of CRC was 92.3% (95% CI, 63.9-98.7%), with similar specificity, whereas the specificity for detecting adenomas was higher, 89.2% (95% CI, 74.6-96.9%). No significant correlations were found between the expression of CD24 and the two SNPs examined. However, preliminary data shows that the P170 C/T variant may increase susceptibility to CR adenomas (p=0.048) while the TG/del CD24 SNP may have a protective role (NS). Conclusions: The CD24 blood test is the first of its kind to be able to detect adenomas. It can also successfully distinguish CRC from healthy subjects. CD24 may serve as a potential and promising biomarker for the early detection of CRC. Larger studies are warranted to establish the future potential of this promising test.