Abstract
Guanylyl cyclase C (GCC) is a transmembrane surface receptor restricted to intestinal epithelial cells, from the duodenum to the rectum. We compared GCC expression in tumors and normal rectal tissues, and investigated the relation between GCC expression and metastasis and long-term survival of rectal cancer patients. Based on the UICC classification, 42 rectal cancer patients in this study were classified as stage I, 48 patients as stage II, and 90 patients as stage III. Overexpression of GCC was observed in 80 rectal tumors as compared to matched normal tissues, where no strong staining of GCC was observed. An association between GCC mRNA in the circulation and tumor emboli in vessels, CK20 mRNA, distant organ metastasis, and survival status was observed in 100 rectal cancer patients. Univariate Cox regression analysis indicated that tumor emboli in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC mRNA correlated with 5-year disease-free survival (DFS); while lymph node metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall survival (OS). In a multivariate Cox regression model, GCC mRNA level and mesenteric root lymph node metastasis associated with DFS, while GCC mRNA levels associated with OS. Quantification of GCC expression in circulation is a valuable biomarker for assessing tumor burden and predicting outcome in rectal cancer patients.
Highlights
Rectal cancer is one of the most common malignancies and causes of tumor-related death worldwide, with an estimated 39,220 new cases in the United States in 2016 [1, 2]
An association between Guanylyl cyclase C (GCC) mRNA in the circulation and tumor emboli in vessels, CK20 mRNA, distant organ metastasis, and survival status was observed in 100 rectal cancer patients
Univariate Cox regression analysis indicated that tumor emboli in vessels, lymph node metastasis, mesenteric root lymph node metastasis and GCC mRNA correlated with 5-year disease-free survival (DFS); while lymph node metastasis, GCC mRNA, and CK20 mRNA strongly correlated with 5-year overall survival (OS)
Summary
Rectal cancer is one of the most common malignancies and causes of tumor-related death worldwide, with an estimated 39,220 new cases in the United States in 2016 [1, 2]. More specific and sensitive biomarkers are needed for screening and detecting colorectal cancer cells. GCC is a crucial tumor biomarker for the identification of occult metastases in lymph nodes and circulation when associated with prognosis of colorectal cancer (CRC) because of its highly restricted expression [11]. Comparisons of multiple epithelial cell markers (CK19, CK20, GCC, and CEA) have demonstrated that GCC is one of the most specific and sensitive markers for detecting circulating CRC cells [12,13,14]. GCC is an important factor in the GUCY2C hormone axis because it promotes proliferation of transit-amplifying cells in crypts, DNA damage repair, and differentiation along the secretory lineage of intestinal and epithelial cells [18,19,20,21]
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