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The Effect Of MiR-21-PDCD4 Signaling Pathway On The Survival Time Of Patients With Stage Esophageal Carcinoma Ⅱ After Operation

Posted on:2018-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:J D ZhangFull Text:PDF
GTID:2334330518479020Subject:Oncology
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Destination1.Finding the expression difference and relativity of micro-21 and PDCD4 in cancer tissues and adjacent normal tissues in patients with stage II esophageal carcinoma after operation.2.analyzing the correlation of clinicopathological features of micro-21 and PDCD4.3.analyzing the the effects of micro-21 and PDCD4 on clinicopathological features during OS and PES respectively.4.Analyzing the diagnostic specificity and sensitivity of miR-21 and PDCD4 in patients with phase II esophageal cancer after 3 years,5 years survival.miR-21 and PDCD4 will be divided into high and low expression groups according to the value of cutoff determined by Youden index,then compare the PFS and OS in two groups.Methods97 specimens were collected from the mesothorax in patients with phase II of esophageal carcinoma in Nanyang First People’s Hospital from January 2010 to January 2013.The postoperative carcinoma tissue and adjacent normal tissues were cut into 5μm thick slices(5 pieces)and 2μm thick slices(for immunohistochemistry);total RNA was extracted in 5μm-thick tissues and the expression level of miR-21 was detected by RT-PCR(real-time fluorescence quantitative polymerase chain reaction);the protein expression level of PDCD4 was detected in 2μm thick slices in carcinoma tissue and adjacent normal tissues.Results1.The correlation analysis revealed a negative correlation(r=-0.41,P=0.00)of MicroR-21 and PDCD4 in the cancer tissues in patients with phase II esophageal carcinoma after operation,but there was a positive correlation(r=0.51,P=0.00)of MicroR-21 and PDCD4 in the normal tissues adjacent cancer tissues.2.There was a positive correlation between microRNA-21 expression level and the depth of invasion,lymph node metastasis or not,and the length of endoscopic lesions(r=0.23,P=0.02;r=0.22,P=0.03;r=0.36,P=0.00),and a negative correlation was existed between microR-21 expression level and differentiation degree(r=-0.60,P=0.00).There was no correlation between microR-21 expression level and age,gender and location of the lesion(P>0.5).The expression level of PDCD4 in cancer tissues showed negative correlation with the depth of invasion,lymph node metastasis or not,and the length of endoscopic lesions(r=-0.21,P=0.04;r=-0.24,P=0.01;r=-0.37,P=0.00),and there was no correlation between PDCD4 expression level and age,gender and location of the lesion(P>0.5).3.The establishment of COX regression model revealed that the tumor invasive depth,lymph node metastasis,differentiation,endoscopic lesion length,microR-21 expression and PDCD4 expression were all risk factors to affect PFS in patients with esophageal squamous cell carcinoma in stage II,and the statistical results are(HR=0.15,P=0.01),(HR=0.19,P=0.00),(HR=1.94,P=0.01),(HR=0.56,P=0.02),(HR=1.70,P=0.00),(HR=0.98,P=0.02)respectively.While the gender,age and location of lesions showed no correlation with PFS of patients with stage II esophageal squamous cell carcinoma after operation(P > 0.05).4.According to the ROC(receiver operating characteristic)curve,the area under the curve of the expression of miR-21 in cancer tissues obtained for 3 years,5 years progression free survival were 73.5%,80.6%,respectively,P< 0.05;and the maximum value of Youden’s index of 3 years and 5 years miR-21 were 0.557 and 0.501 respectively,with the same critical point corresponding cutoff value 0.935,the related sensitivity were 90.5% and 89.2% respectively,the specificity was 65.2% and 60.9% respectively;the area under the curve of 3 years,5 years overall survival prediction were 81%,93.2%,respectively P < 0.05;the related maximum value of Youden’s index were 0.557,0.859,the related critical points were 0.935,0.78,the sensitivity was 90.5% and 85.9% respectively,the specificity was 65.2%,1.The area under the curve of the expression of PDCD4 in cancer tissues obtained for 3 years,5 years progression free survival were 77.3%、78.4% respectively,P< 0.05;and the maximum value of Youden’s index of 3 years and 5 years miR-21 were 0.0.517,0.594,with the same critical point corresponding cutoff value26.5%,31%,the related sensitivity were 64.2% and 67.4% respectively,the specificity was 87.5%;the area under the curve of 3 years,5 years overall survival prediction were 73.2% and 82.7% respectively,P < 0.05;the related maximum value of Youden’s index were 0.359 and 0.663 respectively,the related critical points were 20.5% and 31% respectively,the sensitivity was 44.6% and 66.3% respectively,the specificity was 91.3% and 1 respectively.Conclusion1.The expression level of miR-21 in tumor tissue of patients with phase II esophageal squamous cell carcinoma was higher than that of normal tissues,the expression of PDCD4 protein was lower than that in adjacent normal tissues,miR-21 expression and PDCD4 protein expression was negatively correlated between the two,the higher the expression of miR-21 is,the lower the PDCD4 expression.miR-21 inhibits mRNA of PDCD4 to decrease the protein level of PDCD4.2.The depth of tumor invasion,the length of endoscopy and lymph node metastasis in patients showed positive correlation with the expression of miR-21,while they showed negative correlation with PDCD4 expression.Expression was negatively correlated with the degree of tumor differentiation,but the expression of PDCD4 was positively correlated with the degree of tumor differentiation.3.The PFS of patients with phase II esophageal squamous cell carcinoma after operation was affected by the depth of tumor invasion,the length of endoscopy and lymph node metastasis,miR-21 expression and PDCD4 expression.4.the expression level of miR-21 and PDCD4 in the patients with phase II esophageal squamous cell carcinoma could give assessment on 3 years,5 years progression free survival and overall survival prediction.
Keywords/Search Tags:Esophageal squamous cell carcinoma, PDCD4, miR-21
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