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Expression And Significance Of Axin Protein And RNA Methylation Related Protein Mettl14 In Gastric Cancer

Posted on:2018-07-11Degree:MasterType:Thesis
Country:ChinaCandidate:L ZhaoFull Text:PDF
GTID:2334330515989973Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective: Tumor is that the body under the effect of a variety of carcinogenic factors activate oncogene or inactivate tumor suppressor genes,losing the normal regulation of cell growth and caused by abnormal growths.Axin is Axin gene encoding protein,Axin gene on chromosome 16 p13.3 in human.Studies have shown that Axin proteins can be combined with a variety of signaling molecules and participate in multiple signaling pathways to accelerate the phosphorylation and degradation of ?-catenin and Reduce the concentration of ?-catenin in the nuclei.The ?-catenin is an important hub in Wnt signaling pathway,The study found that Wnt signaling pathways plays an important role on cell proliferation?differentiation?migration,but also to participate in the regulation of stem cells in different developmental stages,which is closely related to the occurrence and development of tumors.Axin protein is an important negative regulatory factors in Wnt signaling pathways,which plays an inhibitory effect on the occurrence and development of tumors.N6-methyladenosine(N6-methyladenosine m6A)is one of the most abundant chemical modification in the m RNA in eukaryotes.Mettl14 is a new methyltransferase which was found in mammals in 2014,it can catalyze methylation modification of mammalian mRNA.Existing research shows that the m6 A plays an important regulatory role on cell differentiation and proliferation?apoptosis.It proves that Mettl14 is closely connected with tumors;Furthermore,the study found that m6 A also have regulation effect on the differentiation of stem cells.So Mettl14 and Axin also may exist a certain correlation about the influence mechanism of the tumors.Gastric cancer is one of the high incidence of human malignant tumors,In our country,the incidence of gastric cancer is 31.28/10,0000,which ranked second,the mortality rate of gastric cancer is 22.04/10,0000,which ranked third.If there is no effective prevention and treatment measures,The incidence and case fatality rate of gastric cancer will rise further in China.Although the basis of gastric cancer is very broad,but there have not been seen in gastric cancer the combined testing about Mettl14 and Axin at present.The research adopts the immunohistochemical method,united detection the expression of Mettl14 and Axin in gastric cancer?precancerous tissue and normal gastric tissues,studying the influence mechanism of both in the occurrence and development of gastric cancer and correlation between them;At the same time to explore the relationship about them and gastric cancer staging ? classification ? tissue differentiation?lymph node metastasis.Methods: We randomly select the surgical excision specimens 50 cases that have been pathology diagnosed of stomach cancer from January 2015 to December 2015 in gastrointestinal surgery of southwest medical university affiliated hospital.Specimens all have complete cancer tissue and normal gastric mucosa tissues,with complete clinical data and pathological data at the same time,which have no radiotherapy?chemotherapy and biological treatment before the operation.We another randomly select the specimens of gastric mucosa 50 cases from January 2015 and December 2015 in outpatient of southwest medical university affiliated hospital,which have been pathology revealed of chronic atrophic gastritis with intestinal metaplasia?low level intraepithelial neoplasia tissue without history of gastric cancer by gastroscopy.We detect the expression of Mettl14 and Axin in gastric cancer and precancerous tissue and normal gastric tissues by immunohistochemical SP method,And statistical analysis the relevant experimental data through SPSS statistics software.Results: The positive expression of Axin have 59 cases and the negative expression of Axin have 18 cases in 77 cases normal gastric mucosa tissues,the positive expression rate is 76.6%;The positive expression of Axin have 40 cases and the negative expression of Axin have 37 cases in 77 cases gastric cancer tissues,the positive expression rate is 51.9%;The positive expression of Axin have 10 cases and the negative expression of Axin have 19 cases in 29 cases gastric mucosal precancerous lesions tissues,the positive expression rate is 34.5%.The positive expression of Axin in normal gastric mucosa tissues respectively compare with in gastric mucosal precancerous lesions tissues and gastric cancer tissues,the difference was statistically significant(P < 0.05);The positive expression of Axin in gastric mucosal precancerous lesions tissues and gastric cancer tissues have no significantly difference(P > 0.05).The expression of Axin in gastric cancer tissues has nothing to do with patients' gender,age,tumor location,classification(P > 0.05),which have closely relate with lymph node metastasis,TNM clinical stage and tissue differentiation(P < 0.05).The positive expression of Mettl14 have 27 cases and the negative expression of Axin have 50 cases in 77 cases gastric cancer tissues,the positive expression rate is 35.1%;The positive expression of Mettl14 have 65 cases and the negative expression of Axin have 12 cases in 77 cases normal gastric mucosa tissues,the positive expression rate is 84.4%;The positive expression of Axin have 10 cases and the negative expression of Mettl14 have 18 cases in 11 cases gastric mucosal precancerous lesions tissues,the positive expression rate is 62.1%;The positive expression of Mettl14 in normal gastric mucosa tissues respectively compare with in gastric mucosal precancerous lesions tissues and gastric cancer tissues,the difference was statistically significant(P < 0.05).The positive expression of Mettl14 in gastric mucosal precancerous lesions tissues compare with in gastric cancer tissues,the difference was statistically significant(P < 0.05).The expression of Mettl14 in gastric cancer tissues has nothing to do with patients' gender,age,tumor location,classification(P > 0.05),which have closely relate with lymph node metastasis,TNM clinical stage and tissue differentiation(P < 0.05).Spearman rank correlation analysis showed the expression of Axin is positively correlation with the expression of Mettl14 in gastric cancer tissues.Conclusion:(1)The positive expression of Axin in normal gastric mucosa tissues is higher than in gastric mucosal precancerous lesions tissues and gastric cancer tissues;The positive expression of Mettl14 in normal gastric mucosa tissues is higher than in gastric mucosal precancerous lesions tissues and gastric cancer tissues.It reminders Axin and Mettl14 may inhibit the occurrence of gastric cancer,which provide new targets for tumor targeting therapy.(2)The positive expression of Axin in gastric mucosal precancerous lesions tissues and gastric cancer tissues have no significantly difference;The positive expression of Mettl14 in gastric mucosal precancerous lesions tissues is higher than in gastric cancer tissues.It reminders that Axin gene may already exist mutations in the precancerous lesions tissues.Jointing detection Axin and Mettl14 can helps screen the precancerous lesions tissues.(3)The expression of Axin and Mettl14 in gastric cancer tissues all has nothing to do with patients' gender,age,tumor location,classification,which have closely relate with lymph node metastasis,TNM clinical stage and tissue differentiation.Tissue differentiation and TNM staging the worse in patients with gastric cancer,Axin positive expression rate is lower.It reminders that Axin and Mettl14 may inhibit the proliferation,differentiation and metastasis of gastric cancer cells.Jointing detection Axin and Mettl14 can provide laboratory basis for the diagnosis of the clinical staging of gastric cancer and prognosis assessment.(4)The expression of Axin is positively correlation with the expression of Mettl14 in gastric cancer tissues,which prompt both have synergy in inhibiting tumor development,Combining targeted therapy both Axin and Mettl14 may improve the safety,effectiveness,and thoroughness of the treatment of tumor.
Keywords/Search Tags:Mettl14, Axin, gastric cancer, immunohistochemistry
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