The object of this proposal is to define the utility of guanylyl cyclase C (GCC) as a marker for the staging and post-operative surveillance of colorectal cancer. In the U.S., colorectal cancer is the fourth most common cancer and the third leading cause of cancer-related death. Staging of cancer is crucial since it determines prognosis and influence management, including the administration of chemotherapy. Current techniques understage many patients due to the unreliable detection of extra-intestinal disease. This is illustrated by the recurrence of disease in 30-50 percent of patients who underwent """"""""curative"""""""" surgery. The main reason is due to the lack of a sensitive and specific method to detect the presence of tumor cells prior to clinically evident recurrence. GCC is specifically expressed in intestinal mucosa and colorectal cancer cells. Preliminary studies demonstrate that expression measured by RT-PCR identifies GCC in colorectal tumor cells in lymph nodes obtained during surgery, and in blood samples from patients with extra-intestinal colorectal cancer. The present study will examine the utility of GCC as a marker for the staging and post-operative surveillance of patients with colorectal cancer.
Four specific aims are proposed: (1) to compare staging of patients with colorectal cancer by GCC RT-PCR with conventional histopathologic staging, (2) to compare the predictive value of staging by GCC RT-PCR versus conventional histopathology for recurrent colorectal cancer, (3) to compare in serial blood samples, GCC RT-PCR versus CEA determination to detect post-operative recurrence of colorectal cancer, and (4) to develop a predictive model for colorectal cancer recurrence.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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Lively, Tracy (LUGO)
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Thomas Jefferson University
Schools of Medicine
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Aka, Allison A; Rappaport, Jeff A; Pattison, Amanda M et al. (2017) Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer. Expert Rev Clin Pharmacol 10:549-557
Kim, G W; Lin, J E; Snook, A E et al. (2016) Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity. Nutr Diabetes 6:e211
Lin, Jieru E; Colon-Gonzalez, Francheska; Blomain, Erik et al. (2016) Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis. Cancer Res 76:339-46
Witek, Matthew E; Snook, Adam E; Lin, Jieru E et al. (2014) A novel CDX2 isoform regulates alternative splicing. PLoS One 9:e104293
Marszalowicz, Glen P; Snook, Adam E; Magee, Michael S et al. (2014) GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer. Oncotarget 5:9460-71
Snook, Adam E; Magee, Michael S; Schulz, Stephanie et al. (2014) Selective antigen-specific CD4(+) T-cell, but not CD8(+) T- or B-cell, tolerance corrupts cancer immunotherapy. Eur J Immunol 44:1956-66
Wilson, Chantell; Lin, Jieru E; Li, Peng et al. (2014) The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer. Cancer Epidemiol Biomarkers Prev 23:2328-37
Hyslop, Terry; Waldman, Scott A (2013) Guanylyl cyclase C as a biomarker in colorectal cancer. Biomark Med 7:159-67
Hyslop, Terry; Waldman, Scott A (2013) Molecular staging of node negative patients with colorectal cancer. J Cancer 4:193-9
Kim, Gilbert W; Lin, Jieru E; Blomain, Erik S et al. (2013) New advances in models and strategies for developing anti-obesity drugs. Expert Opin Drug Discov 8:655-71

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