| Objective: Esophageal cancer is one of the top ten malignant tumors in morbidity and mortality worldwide,and early diagnosis of the disease is not easy and the prognosis of patients is poor.In recent years,studies have found that metadherin(MTDH)is up-regulated in a variety of human cancers,which has been reported to be closely related to the occurrence and development of human cancers.However,the functional significance of MTDH in human esophageal squamous cell carcinoma(ESCC)is still unknown.The purpose of this study was to investigate the role and mechanism of MTDH in ESCC tissue and blood.Methods: 1.The differentially expressed genes MTDH and its co-expressed genes in human ESCC were screened out through bioinformatics analysis of GEO and other databases.2.The differential expression of MTDH in ESCC tissues and normal esophageal mucosal tissues was clarified,and whether the high and low expression of MTDH was associated with the clinical characteristics of patients with ESCC was further explored in public database.3.Public database was also applied to determine the relationship between the expression level of MTDH and the survival of patients with ESCC.4.Go function enrichment analysis and KEGG pathway enrichment analysis were performed on the screened differential genes by using R software to predict the molecular biological mechanism of MTDH in ESCC.5.Public databases were analyzed to generate protein co-expression networks map,and to draw the heat maps associated with micro RNA expression.6.Correlation of genes with signaling pathways,coexpressed protein networks and micro RNA was analyzed.7.QRT-PCR,immunohistochemistry or ELISA were performed for MTDH levels in tissues and serum of patients with ESCC to analyze the relationship between MTDH levels and clinicopathological features.8.KaplanMeier method was used to analyze the relationship between MTDH expression and the prognosis of ESCC patients,and the survival curves of overall survival(OS)and progressionfree survival(DFS)were plotted.9.Prognostic risk factors in patients with ESCC were analyzed using the COX proportional hazards model.10.To analyze its diagnostic efficacy as a serum diagnostic marker of ESCC,and draw ROC curve.Results: 1.Bioinformation analysis showed that MTDH was a differentially expressed gene in ESCC,which was significantly up-regulated and was correlated with tumor stage,prognosis and survival.Patients with high MTDH expression had shorter OS and DFS than patients with low expression in ESCC,both of which were statistically significant(P<0.05).It was predicted that it was involved in multiple signaling pathways and multiple biological processes and functions of tumor development,and was interrelated with a variety of proteins and micro RNAs,with statistical significance(P<0.05).2.The contents of MTDH mRNA and protein in ESCC tissues were higher than those in adjacent tissues(P<0.05).It was significantly correlated with G grade,T stage,M stage,N stage and p TNM stage(P<0.05),and had no correlation with age,sex,smoking history,drinking history,tumor distribution and tumor maximum diameter(P>0.05).3.The OS and DFS of ESCC patients with positive MTDH expression were(16.262±0.855)months and(14.943±0.981)months respectively.The OS and DFS of ESCC patients with negative MTDH expression were(20.533±1.278)months and(19.857±1.436)months respectively.The OS(P=0.014)and DFS(P=0.029)of the patients with positive MTDH expression were significantly lower than those with negative MTDH expression.Univariate analysis showed that T stage(P=0.013),N stage(P=0.028),M stage(P=0.041),p TNM stage(P=0.016)and MTDH expression(P=0.007)significantly affected the prognosis and survival of patients with ESCC.Multivariate analysis further suggested that MTDH was an independent risk factor affecting the prognosis and survival of patients with ESCC(P=0.020).4.MTDH and SCC concentrations in the serum of ESCC patients were higher than those of healthy subjects(P<0.05).Serum MTDH was significantly correlated with N stage,T stage,M stage and p TNM stage of patients with ESCC(P<0.05).There was no significant correlation with other factors.5.Serum concentrations of MTDH in the death group of ESCC were higher than those in the survival group(P<0.001).6.ROC analysis showed that the AUC values of MTDH alone,SCC alone and the combined detection were 0.850,0.821 and 0.927,respectively,with statistically significant differences(P<0.05).Conclusions: 1.The expression of MTDH was significantly increased in the tissues and serum of ESCC,and the level of the expression was correlated with T stage,G grade,M stage,N stage,pTNM stage and poor prognosis of patients with ESCC.Furthermore,the high expression of MTDH is an independent risk factor that affects the prognosis and survival of patients with ESCC.The expression of MTDH in serum may be used as a biomarker for the auxiliary diagnosis of ESCC.2.MTDH may be involved in multiple signaling pathways and multiple biological processes and functions of tumor development in human body,and is interrelated with a variety of proteins and micro RNAs.3.MTDH is involved in the occurrence and development of ESCC,of which is a potential biomarker for the diagnosis,treatment and prognosis. |
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