Colorectal Seromic™ Profiling Assay
Seromic analysis of colorectal cancer markers
It is estimated that there will be approximately 150,000 cases of colorectal cancer in the United States annually with almost 50,000 deaths attributed to this type of cancer, nearly 9% of all cancer deaths.
One of the major unmet needs in colorectal cancer is an accurate staging method to determine how far the disease has spread. Today, the standard method is to examine cell biopsies, which only reflects a very small portion of the tumor. A superior method would be a sensitive, specific, blood-based, noninvasive biomarker-based test for early-stage CRC that does not depend on stool sampling. This has the potential for greater patient compliance, with associated public health benefits and decreased health care costs(1).
SEREX studies identify important antigens
SEREX analysis of four colon cancer cDNA libraries have been carried out. Scanlan et al. (2) identified a total of 234 cDNA clones encoding 48 different antigens. Following sequence analysis, 17 unique genes and 31 known genes were identified. The majority of the proteins were nuclear in origin while the other were metabolic enzymes. One of the more interesting proteins was a mutated version of the p53 tumor suppressor gene (NY-CO-13). An additional two antigens, NY-CO-37 and NY-CO-38 were found to be coded by unique genes mapped to chromosome 113. NY-CO-38 was found to be expressed in some normal tissues but not in normal colon. This protein was found to be expressed in colon cancer and may be the basis for its immunogenicity in cancer patients.
Two additional studies were performed by Line et al.(3) and Ishikawa et al.(4) In the first study, Line, et al. isolated 8 gene products including 2 genes, AD034 and RHAMM, that have been seen in other SEREX studies. RHAMM appeared to be overexpressed in tumor tissue. Ishikawa , et al. isolated 64 genes from colon cancer cell lines. One of the genes, CDX2, carried a frameshift mutation indicating that the immune response raised against tumor-specific sequences.
Antigens in the Colorectal Seromic™ Profiling Assay
Serametrix has now combined important colorectal antigens from the early SEREX work with more recently discovered markers to produce our Seromic™ Profiling Assay for screening patient serum samples. Included in the assay are antigens highlighted in Serametrix biomarker studies as well as recent clinical trials for new melanoma drugs. Further antigens were included from known disease pathways after consultation with experts and comprehensive literature searches.
Figure 1. A panel of cancer testis antigens has been identified at Serametrix and included in the Colorectal Seromic™ Profiling Assay. This proprietary 7-plex was observed when comparing Stage IIA (non-metastatis) colorectal cancer to Stage IV (metastatic).
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1. Mark Han, Choong Tsek Liew,Hong Wei Zhang, SamuelChao, Run Zheng, Kok Thye Yip, Zhen-Ya Song, Hiu Ming Li, Xiao Ping Geng, Li Xin Zhu, Jian-Jiang Lin, K. Wayne Marshall, and Choong Chin Liew, Novel Blood-Based, Five-Gene Biomarker Set for the Detection of Colorectal Cancer, Clinical Cancer Research January 2008 14, 455.
2. Scanlan MJ, Chen YT, Williamson B, Gure AO, Stockert E, Gordan JD, Türeci O, Sahin U, Pfreundschuh M, Old LJ, Characterization of human colon cancer antigens recognized by autologous antibodies, Int J Cancer. 1998;76(5):652-8.
3. Line A, Slucka Z, Stengrevics A, Silina K, Li G, Rees RC, Characterisation of tumour-associated antigens in colon cancer, Cancer Immunol Immunother. 2002;51(10):574-82.
4. Ishikawa T, Fujita T, Suzuki Y, Okabe S, Yuasa Y, Iwai T, Kawakami Y., Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability, Cancer Res. 2003 Sep 1;63(17):5564-72.