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The Study Of Relationship Between Expression Changes Of Stem Cell Markers Before And After Neoadjuvant Chemotherapy And Recurrence And Metastasis In Gastric Cancer

Posted on:2019-03-09Degree:MasterType:Thesis
Country:ChinaCandidate:X Y YangFull Text:PDF
GTID:2334330545453770Subject:Internal medicine
Abstract/Summary:
Background and purposeGastric cancer is one of the most common malignancies in the world.Its incidence and mortality ranked the 4th and 2nd places among cancer of all sites,respectively.It was usually asymptomatic in early stage of gastric cancer,and was diagnosed at advanced stages in which the prognosis is poor.Sor far,many studies have suggested that cancer stem cells participate in tumor formation.Nanog is a heterologous homeodomain protein with typical functions in self-renewal and pluripotent transcriptional regulation.Oct-4 and Sox-2 are key transcription factors that induce pluripotent stem cells and not only regulate normal cell differentiation,but also are closely related to the occurrence and development of malignant tumors.N-cad is a multifunctional cytoplasmic protein and an important regulator of Wnt signaling.E-cad is one of the important adhesion molecules on the cell membrane and plays an important role in cell-cell adhesion and maintenance of cell membrane integrity.In malignant tumors,abnormal expression of E-cad and N-cad may cause the loss of cell adhesion function,resulting in easy infiltration andmetastasis of tumor cells,and play an important role in the development of malignant tumors.In this study,the expression levels of Nanog Oct-4,Sox-2,E-cad and N-cad before and after neoadjuvant chemotherapy of gastric cancer were detected by immunohistochemistry to investigate the relationship between expression changes and postoperative recurrence and metastasis of gastric cancer.Method and MaterialsCollection of clinical pathological data of gastric cancer patients undergoing surgical treatment after neoadjuvant chemotherapy was conducted at the the Affiliated Cancer Hospital of Zhengzhou University during 2012.01-2014.12.Among the 40 cases diagnosed with gastric cancer,two cycles of neoadjuvant chemotherapy and following radical resection was performed.The expression of Nanog,Oct-4,Sox-2,N-cad and E-cad in cancer tissues before and after neoadjuvant chemotherapy using the method of elivision immunohistochemistry.Cancer tissues were sampled through gastroscope and surgical resection before and after neoadjuvant chemotherapy,respectively.The relationship between the expression of Nanog,Oct-4,Sox-2,N-cad and E-cad in the biopsy tissue of gastric cancer before neoadjuvant chemotherapy and clinicopathologic characteristics,and the relationship between the expression changes of each index before and after neoadjuvant chemotherapy and postoperative recurrence and metastasis were analyzed.Factors affecting postoperative recurrence and metastasis of gastric cancer were screened and analyzed.Results1.The expression of Nanog,Oct-4,and Sox-2 before neoadjuvant chemotherapy was related to the degree of differentiation,lymph node infiltration(P <0.05),but not related to gender,age,tumor location,clinical stage and depth of invasion(P > 0.05).2.The expression of N-cad and E-cad before neoadjuvant chemotherapy was related to the degree of differentiation of patients(P<0.05),but not related to gender,age,tumor location,depth of invasion,lymph node infiltration,clinical stage(P>0.05).3.The mDFS and mOS in the tissues with the expression of Nanog,Oct-4 and N-cad increased after neoadjuvant chemotherapy were shorter than those in the down-regulation group and the invariable group(P<0.05).4.There was no significant difference in the mDFS and mOS among the Sox-2up-regulated group and the invariant and down-regulated groups(P>0.05).There was no significant difference in mDFS and mOS among the E-cad expression up-regulation group and the invariant and down-regulation groups(P>0.05).5.The group analysis showed that only the change group of Oct-4 and N-cad in the simultaneous had a shorter mDFS and m OS than the down-regulation group and the unchanged group at the same time(P <0.05).The group Nanog and Oct-4changed simultaneously,the group Nanog and N-cad changed simultaneously,the group Nanog,Oct-4 and N-cad changed simultaneously and there was no significant difference in m DFS and mOS among the three groups(P >0.05).6.Stratified analysis showed that mDFS and mOS of Oct-4 and N-cad up-regulated simultaneously group were shorter than those in the Oct-4 up-regulated group alone,the difference was statistically significant(P<0.05)and the mDFS and mOS of Oct-4 and N-cad up-regulated simultaneously group were shorter than those in the N-cad up-regulated group alone,the difference was statistically significant(P<0.05).7.Multivariate COX regression analysis showed that the expression changes of Nanog,Oct-4,and N-cad before and after neoadjuvant chemotherapy,lymph node metastasis,and differentiation are independent factors influencing the prognosis of gastric cancer(P <0.05).8.Spearman related factors analysis showed that the expression changes of Nanog was positively correlated with the expression of Oct-4 in tissues before and after neoadjuvant chemotherapy(r=0.741,P=0.014).The expression changes of N-cad was positively correlated with the expression of Nanog(r=0.821,P =0.011).The expression changes of N-cad was positively correlated with the expression of Oct-4(r=0.544,P =0.038).9.There was no correlation between the expression changes of E-cad and the expression of N-cad(r=0.143,P=1.728),and there was no correlation with theexpression changes of Nanog,Oct-4 and Sox-2(r=0.268,P =0.828;r=0.212,P=1.558;r=0.165,P=2.454).There was no correlation between the expression changes of Sox-2 and the expression changes of Nanog,N-cad and Oct-4(r=0.132,P=1.648;r=0.182,P=1.358;r=0.157,P=1.516).Conclusions1.Up-regulation of the expression of Nanog,Oct-4 and N-cad in tissues before and after neoadjuvant chemotherapy of gastric cancer,DFS is shorter,and postoperative recurrence is more likely to occur.2.The down-regulation of Nanog,Oct-4 and N-cad expression may be a good indicator of the prognosis of gastric cancer.3.Up-regulation of the expression of Oct-4 and N-cad markers may be a predictor of poor recurrence and metastasis of gastric cancer.
Keywords/Search Tags:Gastric cancer, Neoadjuvant chemotherapy, Nanog, Oct-4, Sox-2, E-cad, N-cad
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