| Background Colorectal cancer is one of the most common malignant tumor of human digestive tract, and its incidence ranks third in the world, which is second only to lung cancer and gastric cancer. currently, on a global scale, the number of new cases of colorectal cancer is about 1 million each year, and about 500000 deaths each year, which account for about10%-15% of all new cases of cancers. its early symptom is not obvious, 50% of patients when see a doctor tumor was late stage and had shifted. Due to the influence of various factors such as pollution of the environment, genetic expression and bad living habits, the incidence of colorectal cancer is higher and higher. Now it is considered that the occurrence and development of colorectal cancer is a complex process which is made up of multiple genes and many steps, involving activation of some oncogene and inactivation of tumor suppressor gene. colorectal mucosa epithelial cells keep the dynamic balance between proliferation and apoptosis under normal circumstances, once the balance is broken, it can appear some pathological change. Now colorectal cancer diagnosis relies mainly on the endoscopic and pathological techniques, and barium enema examination, ultrasound, CT and serum tumor markers. with the development of molecular biology, people have a deeper understanding to the research for colorectal cancer, many researchers have detected that the expression levels of some tumor suppressor genes in colorectal cancer tissue have changed, which prompt that there is a certain relationship with the incidence of colorectal cancer. Solute carrier family member May 8(SLC5A8) is a new candidate tumor suppressor genes which is found in recent years, p53 gene is the tumor suppressor genes that has been researched extensivly.they have certain relations with the occurance and development of colorectal cancer.SLC5A8 gene is found by Rodriguez in 2002, and from human kidney c DNA library cloning identification encoding 610 amino acids in the protein sequence, considereing SLC5 is the eighth member of the family, so it was named SLC5A8. SLC5A8 gene is in human chromosome 12q13-23, coding protein belongs to the members of the family of sodium/glucose transporters, which is the carrier of sodium coupling transfer of short chain fatty acid, lactic acid, niacin, and iodide. SLC5A8 encoding protein distributes brush border membrane in terminal ileum and the whole period of large intestine in intestinal, and it is high expression in the end of the colon and rectum.The expression of SLC5A8 gene is reduced or missing in many human tumors, such as thyroid carcinoma, esophageal cancer, gastric cancer,lung cancer and glioma, at present, the domestic and foreign scholars study that the mechanism of expression declining of SLC5A8 gene is mainly due to of SLC5A8 gene exon1 GPG island methylation and histone acetylation, thus promote the occurrence of tumor.SLC5A8 expresses all transporter substrates, among which the function of butyric acid,propionic acid, and pyruvic acid are as histone acetyl enzyme inhibitors, they can mediate a wide variety of tumor cell apoptosis, which may be the mechanism of inhibiting tumor.Butyric acid, in particular, which is the bacteria fermentation product, it can contribute to the variation of normal colonic epithelial cells, which lead to apoptosis by up-regulating apoptosis genes and down-regulating antiproliferative gene. So the inactivation of SLC5A8 gene might be one of the reasons for colorectal cancer occurrence.P53 gene is reported by Lane in 1979 for the first time, and it is one of the genes that has been researched extensivly at present, it is located in the short arm of human chromosome 17,containing10 exons and 11 introns, encoding a contains protein of 393 amino acids. people know it experienced tumor antigen, oncogene and tumor suppressor genes three stages. p53 gene has wild type and mutant two kinds, wild type p53 is a tumor suppressor gene, it involved in cell cycle regulation, and has an important role in inhibiting tumor proliferation,when wild type p53 changes into mutant p53, it lose the inhibition of cell growth, leading to the onset of tumor.The present study found that the p53 gene has close relationship with about50% of tumor, almost all of the tumor has the p53 gene mutation.Objective We study the expression of SLC5A8 gene and p53 gene in colorectal cancer tissues.Methods use(1) real-time fluorescent quantitative PCR reaction the level of SLC5A8 gene m RNA and p53 gene m RNA in 30 case of patients with colorectal cancer between tumor tissue and adjacent to carcinoma tissues;(2) HE staining detect the glandular tube and cell morphology in the tumor tissue and adjacent to carcinoma tissues of patients with colorectal cancer;(3) immunohistochemisty detect the expression of SLC5A8 gene protein and p53 gene protein of patients with colorectal cancer between tumor tissue and adjacent to carcinoma tissues.SPSS16.0 statistical software was used to statistical analysis, measurement data which accord with normal distribution use mean ±standard deviation( x ±s) to show, and which do not conform to the normal distribution use mean rank, the expression level of SLC5A8 gene m RNA between two groups and expression level of p53 gene m RNA between two groups which accord with normal distribution use the t test, and two groups which do not conform to the normal distribution use Mann-Whitney u parametric test, multigroup use K-ruskal-walls H parametric test,with P < 0.05 for the difference is statistically significant.Result Real-time fluorescent quantitative PCR technology detect(1)30 case of patients with colorectal cancer in which there are 22 cases of patients with tumor tissue of SLC5A8 gene m RNA level is lower than the tissue adjacent to carcinoma; 3 cases of patients with tumor tissues and tissue adjacent to carcinoma of SLC5A8 gene have no expression; 5 cases of patients with tumor tissue of SLC5A8 gene m RNA level is higher than tissue adjacent to carcinoma. there is no obvious statistical significance between the differences of m RNA level in tumor tissues and tissue adjacent to carcinoma and patient’s gender, age, tumor location,tumor stage, lymph node metastasis(p>0.05).(2)30 case of patients with colorectal cancer in which there are 13 cases of patients with tumor tissue of p53 gene m RNA level is lower than the tissue adjacent to carcinoma, 17 cases of patients with tumor tissue of p53 gene m RNA level is higher than tissue adjacent to carcinoma.there is no obvious statistical significance between the differences of m RNA level in tumor tissues and tissue adjacent to carcinoma and patient’s gender, age, tumor location, tumor stage(p>0.05),there is statistical significance in lymph node metastasis(p<0.05).Immunohistochemical technique detect(1) SLC5A8 gene protein expression mainly locates in the cytoplasm of colorectal tissues cells, tissue adjacent to carcinoma cells have a little expression, but colorectal tissues cells have never see clear expression.(2) P53 gene protein expression mainly locates in the cell nucleus of colorectal tissues cells, colorectal tissues cells have some expression, but tissue adjacent to carcinoma cells have never see clear expression.Conclusion(1) SLC5A8 gene expression is declining or missing in colorectal cancer tissues, which prompts that it may be involved in the process of colorectal cancer.(2) p53 gene expression is rising in colorectal cancer tissues, which prompts that it is associated with the occurrence of colorectal cancer, and the main mechanism is probably the p53 gene mutation. |
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