| Pancreatic cancer is a kind of high malignant degree and poor prognosis of digestive system tumors.The American Cancer Society estimates that45,220Americans will be diagnosed with pancreatic cancer in2013, and that38,460will die from the disease, ranks fourth in the malignant tumor mortality, according to the2011tumor registration annual report, the incidence of pancreatic cancer ranks7th in all tumors and mortality rate ranks6th. Pancreatic cancer has the characteristics of short duration, progress fast, highly metastasis potential, high mortality, resistance to conventional treatment. The5-year survival rate is only5%, with a median survival time of only4-6months. Early diagnosis is the key to improve overall efficacy of pancreatic cancer. However, the early diagnostic rate of pancreatic cancer is still very low.It is related to the lack of specific clinical manifestations, low positive rate and poor specificity of pancreatic cancer tumor markers, poor imaging diagnosis and other factors. Currently surgery is still an important means to cure pancreatic cancer. However, the long-term efficacy of surgical treatment of pancreatic cancer alone is not optimistic.It is an inevitable choice to develop an integrated treatment of pancreatic cancer for the biological characteristics.With the deepening development of medical technology,the research of the molecular biomedical in pancreatic cancer led a new era that molecular targeted drugs treatment of advanced pancreatic cancer is becoming a hot topic, although the current basic research in pancreatic cancer has made some progress, there are still many problems, such as the etiology and mechanism of the cancer remains unclear, long cycle of tumor basic research, slow process, and poor reproducibility.Cancer research ultimate aim is to treat human diseases. The cancer research and cell lines from animal studies is gradually transformed into the human tumor, specimens bank is an indispensable medium. Since last century, it has established tumor tissue banks for single disease or multi disease. The operating systems were normalized and standardized. In recent years, some Chinese research institutions have also established tumor banks, but most of there were lack of normalized and standardized operating systems. They start to collect specimens when the need to study with the low degree of standardization and scale. Specimen collection also come to an end after the end of the subject. It is not enough to preserved specimens and collected data.Specimen information did not implement the network, the network cannot be accessed by the lack of a national information platform, it is difficult to achieve information sharing and exchange of tumor internationally; The lack of management and quality control affect further research and use of specimens, resulting in a great waste of resources tumors.On the other hand, due to the low rate of patients with resected pancreatic cancer, causing pancreatic cancer specimens resources shortage, The specimens of pancreatic cancer are limited alone in a hospital or research institute.It is difficult to meet the needs of a large number of follow-up fundamental research.Therefore,establishing standardized pancreatic tumor specimens bank is of great practical significance. Pancreatic cancer is a malignant tumor of epithelial cell origin, with a typical epithelial cell morphology characteristics, whereas the epithelial phenotype in a variety of factors will change the phenotype of mesenchymal cells. Epithelial cells led to increased exercise capacity, gained the ability to walk migration, which is a research hotspot in recent years, the epithelial to mesenchymal transition (EMT).E-cadherin is an epithelial marker protein or an important calcium-dependent transmembrane glycoprotein cell adhesion molecules involved in embryonic development, cell signal transduction, maintenance of epithelial cells of normal morphology and polarity. E-cadherin can also affect the ability of tumor invasion and metastasis via multiple links. E-cadherin connected with catenin to form a functional complex E-cadherin/catenin maintain stability cytoskeleton and it can promote adhesion between epithelial cells, epithelial polarity and maintaining integrity of a structure to maintain. In addition, E-cadherin can inhibit tumor cell production of matrix metalloproteinases (MMPs), to avoid degradation of extracellular matrix, maintaining the integrity of the basement membrane. In recent years, studies have found abnormal expression of E-cadherin or absence of pancreatic cancer cells induced EMT, and tumor occurrence and development are closely linked, decreased E-cadherin protein is an important indicator of EMT, but also could be used as prognostic tumor an indicator.DEC1is a transcription factor, a new member of the family of proteins belonging to bHLH containing basic helix-loop-helix (bHLH) domain, DEC1upregulated in a variety of tumors, and its function is involved in tumor cell proliferation, differentiation, withered different stages of death and aging, but in different tissue types, different origins of tumors and tumor development, DECI have different expression patterns may play a different role, the specific mechanism of tumor occurrence and development of the relationship is unclear. Further, for pancreatic cancer is a malignant tumor hypoxia, hypoxia can lead to changes in the microenvironment of the tumor cells of cytokines is one of the most common cause of EMT, DEC1is a hypoxia regulated gene, means that DEC1may be associated with pancreatic cancer EMT.Part1The establishment of standardized pancreatic cancer tissue bankObjective To establish a standardized pancreatic cancer tissue samples bank and database provides the high quality and sufficient source of specimens for the pancreatic cancer molecular biology research, and cooperate with the national nine large hospital to build a national information platform for the information sharing of patients with pancreatic cancer. Methods Reference standardized procedures to establish bio-banks, to develop and standardize the operational processes system in pancreatic cancer bio-sample collection. Tumor tissues,normal tissues were obtained from pancreatic cancer patients during surgery, and blood samples were also drawn from these patients to extract the serum, plasma and DNA. All the tissue samples were preserve in-80℃refrigerator. Patients with pancreatic cancer database through the network platform is established. Results In reference to the establishment and running of the specimens bank on international model, combined with modern information network platform, the Beijing Union Medical College Hospital as the lead unit, cooperate with nine major nationwide hospitals to establish a national standardized pancreatic cancer biological specimens banks. A total of460fresh tissue and blood samples from25pancreatic cancer patients were collected.12blood samples were also drawn to extract DNA. The quality detection results derived from10randomly selected tissues showed that the rate of A260/A280was calculated about1.8to2.0of total RNA. The percent of pass is 80%. The preservation of RNA is suitable for the next molecule biological research.Conclusions:1.To study and develop a uniform set of specimen collection, processing, management and quality control procedures,and to improve the various registration forms templates build a standardized bank of pancreatic cancer specimens.2.Through the network information platform, to collect information on pancreatic cancer patients diagnosed in the country. To achieve the data sharing by building the national information platform of patients with pancreatic cancer.3.To launched a multi-center technology platform that can unify the use of bank resources for basic research of pancreatic cancer,such as molecular biology, genomics, proteomics, etc. The participating units also are able to carry out a personalized study according to their actual situation, in order to lay the foundation for personalized treatment of pancreatic cancer.Part2The expression and significance of E-cadherin,DECl in pancreatic cancerObjective Roles of EMT in pancreatic cancer were evaluated by investigating the expression of E-cadherin,DEC1in normal pancreatic tissue, pancreatic cancer and their correlation. And their relation to clinicopathological features and prognosis were observed.Methods A total of35patients who were confirmed pancreatic ductal adenocarcinoma by pathology report were evaluated in Guangdong General Hosipital in March2008to October2012, and one of the20cases of adjacent normal pancreatic tissue were selected as a control group. The paraffin tissue sections were provided by the department of Pathology. Detected the expression of E-cadherin and DEC1in using immunohistochemical SP method in normal pancreatic tissue and pancreatic cancer and their correlation.To observe the staining of tissue sections by using Olympus microscope and analyse the image by using Image-Pro Plus (IPP6.0) professional image software. the clinical and pathological factors affecting the survival rate of pancreatic cancer were observed by using univariate and multivariate survival analysis.Results1. DEC1were expressed mainly in the cytoplasm of pancreatic cancer, some of the nuclei of the gland is also positive, brownish yellow diffuse distribution, part of the normal pancreatic tissue have yellow diffuse cytoplasmic distribution, but in most normal pancreatic tissue DEC1protein expression were negative or weakly positive, The expression of DEC1were significantly higher in pancreatic cancer than in normal pancreatic tissue (t=-3.179, P<0.01), but the expression of DEC1was not relatian to gender, age, preoperative CA199values, tumor location, tumor size, peripancreatic infiltration, vascular invasion, lymph node metastasis, TNM stage and tumor differentiation and survival time.2. E-cadherin were expressed mainly on normal pancreatic acinar and ductal epithelial cell membrane, brownish yellow membranous distribution, in most pancreatic tissue loss of expression of E-cadherin, membrane staining decreased or disappeared, some of E-cadherin in pancreatic cancer expression is located in the cytoplasm, E-cadherin expression in normal pancreatic tissue was significantly higher than that of pancreatic tissue (t=6.303, P<0.01); The expression of E-cadherin expression was not relatian to gender, age, preoperative CA199values, tumor location, tumor size, peripancreatic infiltration, vascular invasion, TNM stage and tumor differentiation and survival time. And there is the lower expression of E-cadherin in patients with lymph node metastasis than those without lymph node metastasis (P=0.028, P<0.05).3. The expression of E-cadherin and DEC1in pancreatic cancer have no statistical correlation with a Pearson correlation (R=0.128, P=0.464)4. Univariate analysis showed that patients with pancreatic cancer survival rates was not relatian to gender, age, tumor location, peripancreatic infiltration, lymph node metastasis, vascular invasion, TNM stage, tumor differentiation, but tumor size (P=0.014), preoperative CA199levels(P<0.001). Multivariate analysis by establishing Cox regression model found tumor size, preoperative CA199levels were independent factors affecting the prognosis of patients with pancreatic cancer.Conclusions1.The Reduction of E-cadherin protein confirmed the existence of the phenomenon of EMT in pancreatic cancer, and played an important role in lymph node metastasis of pancreatic cancer, The increase expression of DEC1protein in pancreatic cancer, but the relationship with EMT is unclear, need further study.2.Tumor size,preoperative CA199level are independent factor affecting the prognosis of pancreatic cancer... |
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