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Analysis Of Predisposing Factors Of Postoperative Complications And The Differential Expression Of Key Genes In Staging Of Esophageal Carcinoma

Posted on:2018-01-13Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z ZhuFull Text:PDF
GTID:2334330542969933Subject:Clinical Medicine
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Objective:Esophageal carcinoma is a kind of malignant disease with high incidence and mortality in China and even worldwide.Herein,the predisposing factors of postoperative complications of esophageal cancer and the different genetic expression of mRNA,DNA methylation and mutations with different esophageal cancer staging will be analyzed.Methods:A total of 706 patients with esophageal cancer from the First Affiliated Hospital of Nanjing Medical University from 2010 to 2013 and 2015 to 2016 were retrospectively staged according to the AJCC 2012 staging criteria.9 postoperative complications were involved in this study,including lower respiratory tract infection(LRTI),atelectasis(AT),pleural(pericardial)effusion(PE),arrhythmia(AR),Pulmonary embolism(PEM),septicemia(SEP),Anastomotic fistula(AF),chylous leak(CL),pyloric obstruction(PO).Multivariate analysis was used to explore factors,which could be potentially related to 9 postoperative complications.Data of 117 mRNA expression level,122 DNA methylation level and mutation genes from 107 patients with esophageal cancer were obtained from the Cancer Genome Atlas(TCGA)database after deleting 57 patients without necessary information from 164 patients.In addition,all the cases were staged according to the AJCC 2012 staging criteria,further classified I,II as group A(non-advanced),?,? as group B(advanced).After the Propensity Score Matching(PSM),an independent sample T test was used to analyze the differences of mRNA and DNA methylation between group A and B.Additionally,the Spearman correlation analysis was used to analyze the differences of gene mutation between the two groups.Results:Among the 706 patients,524 were male(74.2%)and 182 were female(25.8%).At the time of surgery,their minimum age and maximum age were respectively 32 and 86 years old and the median age was 62 years old.There were 32 cases of adenocarcinoma,659 cases of squamous cell carcinoma and 15 cases of neuroendocrine cancer.Additionally,the numbers of cases with TNM staging from 0 to IV were respectively 39,151,241,270 and 5.Among the 9 postoperative complications,the total numbers(incidence)of each case of LRTI,AT,PE,AR,PEM,SEP,AF,CL and PO were 289(40.9%),24(3.4%),464(65.7%),129(18.3%),0(0),2(0.3%),12(1.7%),4(0.6%)and 1(0.1%).The analysis showed that age was associated with SEP(p =0.011),and pTNM staging was associated with the occurrence of AF(p = 0.010)and CL(p = 0.030).The postoperative nutritional pattern was also significantly associated with the occurrence of AF(p = 0.041).There was a significant difference in the expression of EPHA3 mRNA in patients with esophageal cancer between group A and B,and the expression level was higher in group B(p=0.006).There was also a significant difference in DNA methylation level of NOTCH1,of which expression was higher in group B(p = 0.027).The mutations with significant differences between two groups were ZNF750(p = 0.037)and MALAT1(p = 0.044),both of which had higher incidence in group A.Conclusion:Surgery is an important treatment for esophageal cancer,while esophageal cancer patients may occur one or more postoperative complications,among which could be associated with patients' age,TNM staging and postoperative nutritional patterns.The expression of EPHA3 mRNA and the DNA methylation of NOTCH1 were different in different TNM stages of esophageal cancer,and both of them were higher expressed in advanced patients.Mutation of ZNF750 and MALAT1 was negatively correlated with the staging of esophageal carcinoma.
Keywords/Search Tags:esophageal cancer, postoperative complications, predisposing factors, tumor staging, mRNA, DNA methylation, gene mutation, expression level
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