The Significance Of Secretagogin In The Progress And Prognosis Of Colorectal Cancer

Colorectal cancer (CRC) is a general vicious digestive system carcinoma, the World Cancer Association in 2014 showed that the morbidity and mortality of colorectal cancer is still ranked third.Secretagogin was identified in 2000 by Wagner using immune screening technology in human pancreatic βcells cDNA library. The gene is located on chromosome 6 p22.1-22.3, encoding a 32KDa protein containing 276 amino acids. The protein contains six EF-hand calcium rings according to the protein amino acid sequence analysis, belonging to the S100 protein family. The secretagogin gene is expressed in abundance in pancreas, pituitary, brain, adrenal gland, thyroid gland and the gastrointestinal tract in human. Secretagogin is the first screened protein that is down-regulation in colorectal cancer in our laboratory and has been verified by western blotting and immunohistochemistry. At present the function of the protein is not very clear. Studies have shown that the secretagogin protein has an influence on cell growth and differentiation. Immunohistochemical results show that secretagogin is mainly expressed in base layer of normal colorectal mucosa fossae, a cone-shaped cell morphology, and is very similar to gut neuroendocrine cells. It has been verified that secretagogin is a very good neuroendocrine marker.Neuroendocrine cell differentiation (neuroendocrine cell differentiation, NED) phenomenon has been confirmed in a variety of adenocarcinoma of non-neuroendocrine organs, and differentiated neuroendocrine cells exist in the form of a single cell or cell nests dispersed, as a composition coupling with cancers. So it is called adenocarcinoma accompanied by neuroendocrine differentiation. It is reported that this kind of malignant tumor includes esophageal cancer, gastric cancer, colorectal cancer, prostate cancer, breast cancer, etc. Here we mainly explore the significance of secretagogin in the progress and prognosis of colorectal cancer.Recent reports show that secretagogin will induce chemical resistance by the inhibition of the apoptosis in small cell lung cancer cell. In renal clear cell carcinoma, the high expression of secretagogin is associated with high metastasis. As opinions vary, the relationship between the neuroendocrine differentiation with prognosis in adenocarcinoma is not clear. Studies showed that the clinical significance of adenocarcinoma accompanied by endocrine differentiation patients is associated with primary sites.Some argue that endocrine differentiation would indicate a good prognosis in the patients with pancreatic cancer, while a bad prognosis would be indicated in prostate cancer with neuroendocrine differentiation. At the same time, there have been reports that neuroendocrine differentiation takes no exact influence on the prognosis of breast cancer. In colorectal cancer, researches about the relationship between neuroendocrine differentiation and prognosis still hold controversial, but most of the researches indicated neuroendocrine differentiation suggests a poor prognosis. Grabowski found that differentiation of neuroendocrine cell can be used as predicting the late phase (III, IV) as independent prognostic indicators in patients with colorectal cancer. NE cell differentiation would be more likely to appear in the poorly differentiated adenocarcinoma compared to the medium or well differentiated adenocarcinoma. So in colorectal cancer, is SCGN related with the chemotherapy drug resistance or high metastasis?To confirm the above assumptions, we first tested the expression of SCGN in 417 tissue samples of colorectal cancer patients. Then we constructed an SCGN-overexpressed cell line and explored whether SCGN takes effects on the drug resistance in colorectal cancer cell or not. Results show that expression of SCGN in 417 cases of tissue samples does not influence prognosis, P=0.230. Interestingly, expression of SCGN was significantly positively related with prognosis in patients after chemotherapy, P=0.004. In addition, in these samples, SCGN is significantly positively related with the expression of membrane E-Cadherin, P values were 0.018. In the SCGN-overexpressed cell lines which we construced, SCGN enhanced the drug sensitivity. In addition, the overexpression of SCGN promoted invasion, migration capacity in CRC cells. At the protein level and mRNA level, expression of epithelial markers such as E-Cadherin increased significantly.Based on the above data, we draw the following conclusions:1. Expression of secretagogin suggests a good prognosis in CRC patients with chemotherapy. Secretagogin may enhance the sensitivity of colorectal cancer cells to 5-fluorouracil.2. Secretagogin may inhibit colorectal cancer cell migration and invasion ability.