Abstract
Cancers of the colon and rectum are the second leading cause of cancer death among adult Americans. When detected at early stages, colon cancer is highly curable. Colonoscopy, an effective but invasive screening test, has been limited in its public acceptance. The goal of this study was to identify novel serum markers of colon cancers and precancerous colon adenomas as potential candidates for noninvasive detection of early colon neoplasms. Employing expression microarrays, we identified colon cancer secreted protein-2 (CCSP-2) as a novel transcript whose expression is generally absent in normal colon and other normal body tissues, but that is induced an average of 78-fold in Stage II, III, and IV colon cancers, as well as in colon adenomas and colon cancer cell lines. These findings were validated by real-time PCR analysis in an independent panel of colon cancer cases. Moreover, CCSP-2 was shown to encode a secreted protein that circulates stably and is detectable in the blood of mice bearing human cancer xenografts transfected with epitope-tagged CCSP-2. As a novel secreted protein that is markedly induced in colon adenomas and cancers, CCSP-2 is a novel candidate for development as a diagnostic serum marker of early stage colon cancer.
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Acknowledgements
This work was supported by Public Health Service Grants U01 CA88130 (SDM), P30CA43703 to the CWRU/Ireland Comprehensive Cancer Center, and by grant from the National Colon Cancer Research Alliance and Entertainment Industry Foundation, and by grant from the State of Ohio Biomedical Research and Technology Transfer Commission (BRTT). The content reflects the views of the Grantee and does not necessarily reflect the views of the BRTT. SDM is an investigator of the Howard Hughes Medical Institute. We thank James D Lutterbaugh for work on RNA preparation for the microarray experiments. We also thank Ronald M Rerko for assistance with the in vivo mouse studies.
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Xin, B., Platzer, P., Fink, S. et al. Colon cancer secreted protein-2 (CCSP-2), a novel candidate serological marker of colon neoplasia. Oncogene 24, 724–731 (2005). https://doi.org/10.1038/sj.onc.1208134
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DOI: https://doi.org/10.1038/sj.onc.1208134
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