| Colon cancer is the common malignant tumor of digestive tract, which incidence is increasingly year by year. Currently, because of the pathogenesis of colon cancer is unclear, we cannot treat the patients base on the pathogenesis, so early diagnosis becomes the key to improving the prognosis of patients. However, the vast majority of patients with early colon cancer almost have no specific performance. The disease already developed advanced period when confirmed diagnosis. On the aboard, generally check X-ray barium meal and colonoscopy census, making early diagnosis rate was significantly increased, but patients suffering large, costly and poor compliance, this is clearly not the best choice. For these patients with advanced disease, chemotherapy has become the main treatment for such patients, while 5-FU chemotherapy drugs are the main force of colon cancer. Therefore, it is significant to seeking to predict the behavior of biological markers in the diagnosis and treatment of colon cancer actively.UHRF1(ubiquitin-like with PHD and ring finger domains 1) is a hot topic protein of epigenetic research in recent years, which plays an important role in maintaining DNA methylation, and overexpressed in a variety of tumor cells, and have close relationship with tumor occurrence, development, invasion, metastasis and resistance to chemotherapy and radiotherapy. UHRF1 contains multiple protein domains, which could interact with DNA methyltransferase, histone deacetylase, histone methyltransferase to positive regulate DNA methylation, histone acetylation and methylation, that is an important epigenetic regulatory factors. Epigenetics is an emerging rapid developing branch of genetics in recent years, which in the case studies do not involve changes in the nucleotide sequence of the gene to produce a biological phenomenon heritable variation. Wherein the histone modifications and DNA methylation are two important epigenetic research, which played an important role in gene expression, X chromosome inactivation, cell regulation, embryonic development and cancer and so on.DPD is the rate-limiting enzyme of 5-FU catabolism, that will be reduced to dihydro-fluorouracil(FUH2) in the participation of cofactor NADPH; then FUH2 open the cyclic structure in the role of dihydro-fluorouracil enzyme that produced the 5-fluoro-dihydropyrimidine enzyme-β- ureide acid(FUPA); the final form of 5-fluoro-β- alanine(FBAL) by the effect of β-alanine synthase catalytic which excreted by the kidneys. More than 80% of 5-FU in the liver and other tissues break down when they run into the body, and only a very small proportion of 5-FU participate in anabolic that decided to cytotoxicity. As a key decomposite enzyme of 5-FU, DPD activity will determine the level of anabolism and generation into the anabolic nucleotide analogs of 5-FU. DPD is not only an important enzyme of fluoropyrimidine exerting cytotoxic effect, but also a potential indicators predicting tumor sensitivity to chemotherapy drugs of fluorouracil, so it could applied clinical research.Ki-67 is one of the most widely used cell proliferation marker currently, which its amount varies with the cell cycle, which is not expressed in quiescent cells and is widely expressed in proliferating cells, and which is mainly used to evaluate cells. The study show that Ki-67 can be used for judge benign and malignant tumors and malignant degree, and it is closely related with malignant primary tumor size, depth of invasion, metastasis, clinical stage, survival time, recurrence and prognosis.Objective:To investigate the expressions of UHRF1, DPD and Ki-67 protein in colon cancer and normal colon tissue, and to explore the relationship between their expression levels in colorectal cancer and its correlation with clinicopathological features, and to explore the possibility of UHRF1 become new molecular targets of colon cancer, and to explore DPD forecast the association with chemotherapy and drug resistance in colon cancer. It provides the basis of guiding individual treatment and improving prognosis and drug sensitivity in colon cancer.Methods:Collect 100 cases of pathological wax block, including 70 cases of colon cancer tissue and 30 cases of normal colon tissue, and every case had not received preoperative, chemotherapy, radiotherapy, and immune therapy. By applying immunohistochemical methods Envision two-step to detect the expression of UHRF1, DPD, Ki-67 in colon cancer tissues, to analyze statistically the correlation among them with the patients’ sex, age, tumor size, tumor differentiation, TNM stage, lymph node metastasis and depth of invasion and so on. The date were processed by applying SPSS 19.0 statistical software, categorical data using χ2 test, correlation using Spearman relevance measurement, α=0.05 using as the test standard; adopting P < 0.05 for the varinace having statistically significance.Results:1. UHRF1, DPD and Ki-67 were expressed in colon cancer tissues and normal colon tissues. UHRF1 expression localized in the cytoplasm and cell membrane, and the expression levels of UHRF1 in colon cancer tissues was 87.1%(61/70), obviously higher than that of cancer-adjacent normal tissues, which was 56.7%(17/30), the difference was statistically significant(χ2=11.366, P = 0.001); DPD expression localized in the cytoplasm, and the expression levels of it in colon cancer tissues was 84.3%(59/70), dramatically higher than that of the cancer-adjacent normal tissues, which was 20.0%(6/30), the difference was statistically significant(χ2=38.148,P=0.000); Ki-67 expression localized in the cell nucleus, and the expression levels of it in colon cancer tissues was 67.1%(47/70), obviously higher than that of cancer-adjacent normal tissues, which was 26.7%(8/30), the difference was statistically significant(χ2=13.901,P=0.000);2. The expression of UHRF1, DPD and p53 were associated with Dukes stages, the depth of invasion lymph node metastasis, the difference was statistically significant(P <0.05). However, they were irrelevant with the age and gender of patients, as well as the size and histological grading of tumors, the difference was no statistically significant(P> 0.05).3. The expression of UHRF1 and Ki-67 showed a positive correlation between the two proteins(r = 0.367, p = 0.002); The expression of DPD and Ki-67 showed a positive correlation between the two proteins(r = 0.283, p = 0.018); The expression of UHRF1 and DPD showed a positive correlation between the two proteins(r = 0.069, p = 0.572), but have not statistically significant, so the experiment cannot explain a positive correlation between UHRF1 and DPD.Conclusion:The expression of UHRF1, DPD and Ki-67 in colon cancer was dramatically higher than that in normal colon tissues, indicating that they could be sensitive index to detecting in the chemotherapy of colon cancer, and the expression of UHRF1, DPD and Ki-67 in colon cancer were associated with tumor pathology grading and clinical stage. The lower of pathological grade and the later clinical stage, the rates of positive expression of them were higher. It implies that the three proteins expression was correlated with development and drug resistance of colon cancer; The expression of UHRF1 and Ki-67 showed a positive correlation between the two proteins, and the expression of DPD and Ki-67 showed a positive correlation too, however, the expression of UHRF1 and DPD was not statistically significant. UHRF1 expected to become a new target for diagnosis and determine the efficacy of colon cancer. DPD could be an index to judge fluorouracil sensitivity and resistance in progress of treat colon cancer. Detected UHRF1 and Ki-67 or DPD and Ki-67 simultaneously may act as an important indicator of individual development of chemotherapy, sensitivity to chemotherapy and prognosis testing in colon cancer. |
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