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Expression And Clinical Significance Of MiR-135b?LZTS1??-catenin In Pancreatic Cancer

Posted on:2017-08-13Degree:MasterType:Thesis
Country:ChinaCandidate:B L ZhangFull Text:PDF
GTID:2334330488959517Subject:Internal Medicine
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Pancreatic cancer accounts for 8%~10% of digestive malignant tumor,and its main pathological type is pancreatic ductal adenocarcinoma,which accounts about95%.It is the fourth commenest cause of cancer-related death in Western societies,with an overall 5-year survival rate that has remained less than 6%.Due to a highly invasive form,lack of specific symptoms,qick development and serious drug resistance,more than 80% of PC patients have occurred metastasis at the time of diagnosis,which makes surgical and medical methods mostly unsuccessful,resulting in high mortality and poor prognosis.Therefore,to explore the pathogenesis of pancreatic cancer and search for new diagnostic markers and therapeutic targets become a focal and difficlut task for human being which needs to be solved.Micro RNAs is one of the most important researches in recent years.It refers to a kind of small RNA molecules controlling coding gene expression,which could participate in a series of biological processes such as cell proliferation, differentiation,invasion,metastasis and apoptosis,etc.Mi R-135 b,as one of the members of mi RNAs family,is highly expressed in many malignant tumors and affect their malignant biological behaviors through regulating the expression of its downstream target gene.The latest reseach reports that mi R-135 b is also elevated expression in pancreatic cancer.However,the efffect of mi R-135 b and its relative molecular machanism inpancreatic cancer reman unknown,which need to be further studied.Leucinezipper putative tumor suppressor1(LZTS1),as a new candidate tumor suppressor gene,has been confirmed as direct target gene of mi R-135 b in non-small cell lung cancer and cutaneous aquamous cell carcinoma.Many studies have found that LZTS1 protein is positive expressed in normal tissues,but is decreased or absent in tumors.How the expression of LZTS1 protein in pancreatic cancer is rarely reported. Additionally,LZTS1 could indirectly inhibit the Epithelial-Mesenchymal Transition(EMT) by up-regulating the expression of E-cadherin and ?-catenin protein,which inhibits the formation and development of tumor.As known as a highly invasive malignant tumor,the pathogenesis of pancreatic cancer is concealed,and the majority of patients during the diagnosis has been advanced and lost the surgery opportunity.Thus,it is important to further stuy the mechanism of pancreatic cancer for early-diagnosis and improving the prognosis.However,the reseach about mi R-135 b,LZTS1 as well as ?-catenin is lack reported.Aim:To investigate the expression of mi R-135b?LZTS1 and ?-catenin in pancreatic cancer in attempt to explore their correlation and clinical significance.Methods:1.Locked nucleic acid in situ hybridization(LNA-ISH) and immunohistochemistry were used to detect the expression of mi R-135 b,LZTS1 and ?-catenin protein in 70 pancreatic cancer tissues and its adjacent normal tissues, respectively.2.SPSS17.0 stastical package is used to analyze all the dates,and stastical methods contain the Chi-aquare test and Spearman correlation analysis,and the difference is statistically significant when P<0.05.Results:1.The result of ISH shows that the positive rates of mi R-135 b expression in pancreatic cancer and correspongding adjacent noncancerour tissues were71.4%(50/70) vs 42.9%(30/70).The result of immunochenmistry shows that the positive rates of LZTS1 protein were 34.3%(24/70)vs 68.6%(48/70),the rates of?-catenin protein were 34.3%(24/70)vs 74.3%(52/70).The three groups have statistical significance(P<0.05).2.Spearman correlation analysis shows that expression of mi R-135 b had a negative correlation with that of LZTS1 in pancreatic cancer(r =-0.61,P < 0.05), but mi R-135 b expression had no signifiant correlation with ?-catenin(r = 0.06,P > 0.05).LZTS1 expression had a positive correlation with that of ?-catenin(r = 0.37, P<0.05).3. Expression of mi R-135 b, LZTS1 and ?-catenin was closely related with tumor invasion, lymph node metastasis and clinical stage(P < 0.05), but had no correlation with patient age, sex, tumor size,location or histological grade(P > 0.05).Conclusion:Mi R-135 b is highly expressed in pancreatic cancer, while the expression of LZTS1 and ?-catenin is decreased. LZTS1 had a negative correlation with that of Mi R-135 b,and had a positive correlation with that of ?-catenin.In addiction,they are also associated with TNM stages and lymph node metastasis. So we speculate that up-regulated expression of mi R-135 b may participate in the development of pancreatic cancer by down-regulating the expression of LZTS1 protein.
Keywords/Search Tags:Pancreatic cancer, MiR-135b, LZTS1, ?-catenin, In situ hybridization, Immunohistochemistry
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