| Objective: The expression and methylation of engulfment and cell motility1(ELMO1)will be discussed in gastric cancer,which can understand the clinical significance of ELMO1 for gastric cancer.Meanwhile,the potential mechanism of ELMO1 gene will be explored in the occurrence and development of gastric cancer,which can provide the theoretical basis for targeted therapy of gastric cancer.Methods: By analyzing the mRNA expression data of ELMO1 in the TCGA database,the research compared the expression of ELMO1 in gastric cancer and normal gastric samples,analyzed the relationship between ELMO1 mRNA and the clinical pathological characteristics of patients with gastric cancer,and assessed the diagnostic value of ELMO1 mRNA expression in gastric cancer by using the receiver operating characteristic curve(ROC).And by analyzing the methylation information of the promoter region of ELMO1 gene in the SMART online database,the research compared the methylated degree of the promoter region of ELMO1 gene between gastric cancer and normal gastric samples,and analyzed the correlation between the methylated degree of the promoter region of ELMO1 gene and its gene expression in gastric cancer.Meanwhile,we collected the paraffin specimens in our hospital,which was clearly diagnosed with 35 cases of gastric cancer and 17 cases of benign gastric lesions.And the immunohistochemical staining method was used to discover differential protein exprossion of ELMO1 between gastric cancer and normal gastric tissue.And then we analyzed the relationship between ELMO1 protein expression and clinical parameters of gastric cancer patients.In addition,the diagnostic significance of ELMO1 protein expression was evaluated in gastric cancer by ROC curve.Not only that,we used DNA methylation-specific PCR(MSP)to explore the methylation status of the promoter region of ELMO1 gene in gastric cancer and normal gastric tissue respectively,which could understand the methylation-positive rates of the promoter region of ELMO1 gene,and compare the methylation difference between gastric cancer and normal gastric tissue.Meanwhile,we could analyze the correlation between the methylation status of promoter region of ELMO1 gene and its protein expression in gastric cancer.Finally,the ELMO1 gene interaction network was constructed by using the Gene Mania online website,and the GESA database was used to analyze the high expression of ELMO1 gene that might participate in these signaling pathways,which influenced the occurrence and development of gastric cancer.Results: 1.By analyzing the ELMO1 mRNA expression in the TCGA database,it was found that:(1)compared with normal gastric samples(n=32 cases),ELMO1 mRNA expression was highly expressed in gastric cancer(n=375 cases)(P<0.01);(2)clinical pathological feature analysis showed that ELMO1 mRNA expression was related to age,depth of invasion,clinical stage,histological grade,and histological type of patients with gastric cancer(P<0.05),but was not statistically significant with sex,ethnicity,Hp infection,lymph node metastasis,distant metastasis and tumor residue of patients with gastric cancer(P>0.05);(3)ROC curve showed that ELMO1 mRNA had certain diagnostic value for gastric cancer(AUC=0.645).2.By analyzing the methylation data of the promoter region of ELMO1 gene in the SMART online database,it was found that:(1)the methylated degree of the promoter region of the ELMO1 gene was partially higher in gastric cancer than that in normal gastric samples(P<0.05);(2)the correlation analysis between the methylated degree of promoter region of ELMO1 gene and its expression showed a negative correlation in gastric cancer samples(r=-0.49).3.Immunohistochemical test results was showed:(1)ELMO1 protein expression was mainly localized in cell membranes or/and cytoplasm,and the expression level of ELMO1 protein in gastric cancer tissue(n=35 cases)was higher than that in normal gastric tissue(n=17 cases)(P < 0.001);(2)clinical pathological parameters analysis showed that ELMO1 protein expression was not related with sex,age,tumor location,tumor size,degree of differentiation,depth of invasion,lymph node metastasis,distant metastasis,TNM staging,tissue necrosis,vascular infiltration,nerve invasion and expression of CK7,Ki-67 and HER2 of patients with gastric cancer(P>0.05);(3)ROC curve showed that ELMO1 protein had high diagnostic significance for gastric cancer similarly(AUC=0.942).4.Tissue paraffin specimen MSP results were showed that:(1)the methylation-positive rates of the promoter region of ELMO1 gene in gastric cancer tissue(25.7%)was higher than that in normal gastric tissue(0%),but the difference was not statistically significant(P>0.05);(2)there was no statistical significance between the methylation status of the promoter region of ELMO1 gene and its protein expression in gastric cancer(P>0.05),but they still had a feeble negative correlation(r=-0.258).5.By using the Gene Mania online website built the ELMO1 gene interaction network,it was showed that the ELMO1 gene was most closely related to the Dock2,Dock1 and Rac2 gene,and there was a pathway association.At the same time,GSEA enrichment analysis showed that high expression of ELMO1 gene might affect the occurrence and development of gastric cancer by regulating the signaling pathways such as cell cycle,DNA replication,P53,mismatch repair,chemokines and so on.Conclusions: 1.ELMO1 is highly expressed in gastric cancer,and its expression level is inversely correlated with methylation in its promoter region,which may have the potential to become a novel molecular marker for gastric cancer diagnosis.2.Bioinformatics analysis suggests that high expression of ELMO1 gene may affect the occurrence and development of gastric cancer by regulating the signaling pathways such as cell cycle,DNA replication,P53,mismatch repair,chemokines,Rho-GTP and NF-κB. |
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