Expression Of MTHFD2 In Esophageal Squamous Cell Carcinoma And Its Clinical Prognostic Significance

BackgroundEsophageal cancer ranks sixth worldwide in cancer-related deaths.Recently,investigations showed that about 450 000 new patients were diagnosed with esophageal cancer each year,causing approximately 400 000 deaths worldwide.Therefore,esophageal cancer is a disease with high incidence rates and poor prognosis.China is a high-risk area for esophageal cancer,and the pathological type of most patients is esophageal squamous cell carcinoma(ESCC).The high incidence of esophageal cancer in China may be closely related to residents' living habits.Because esophageal cancer is difficult to detect in the early stage,most patients are already in the advanced stage when diagnosed,and cannot undergo radical surgery.In recent years,advances in molecular biology have improved cancer treatment and more and more targeted drugs have gradually begun to appear.The vast majority of targeted drugs have been exploited for treatment of tumors.However,due to the pathology of esophageal adenocarcinoma in western developed countries,the discovery and study of esophageal squamous cell carcinoma targeting drugs are relatively limited.New therapeutic targets and prognostic biomarkers are urgently needed to improve the prognosis of patients with esophageal squamous cell carcinoma.Methylenetetrahydrofolate dehydrogenase 2(MTHFD2)is a key enzyme involved in folate metabolism,which is involved in cell proliferation.Therefore,we speculated that MTHFD2 might be involved in the proliferation of tumor cells.Previous studies have shown that MTHFD2 was closely related to the development and progression of a variety of cancers and to the prognosis of patients.However,few studies have explored the expression of MTHFD2 in esophageal squamous cell carcinoma and its prognostic significance.We conducted this trial to study the relationship between the expression of MTHFD2 and the prognosis and clinicopathological parameters of patients.We explored whether MTHFD2 might be a therapeutic target for esophageal squamous cell carcinoma.Material/Methods:Firstly,the expression of MTHFD2 m RNA in esophageal squamous cell carci noma and its relationship with the overall survival(OS)of patients were predicted in advance through Oncomine database and TCGA database.Then,immunohistochemistry(IHC)was used to detect the expression of MTHFD2 in esophageal squamous cell carcinoma tissues and corresponding adjacent normal tissues.The expressions of ki67 and p53 in ESCC tissues were detected by immunohistochemistry,to investigate whether the expression of MTHFD2 is correlated with the expression of ki67 and p53.Further,MTHFD2 expression level in ESCC and its correlations with patients' clinicopathological characteristics and survival prognosis were investigated,to determine the significance of MTHFD2 in esophageal squamous cell carcinoma.ResultsThe enhanced expression of MTHFD2 was observed in ESCC specimens compared with adjacent normal tissue.The increased expression of MTHFD2 was closely related to pathological grading(P=0.020)and tumor TNM stage(P=0.019).In addition,patients with high expression of MTHFD2 had worse survival than those with low MTHFD2 expression(P<0.05).High expression of MTHFD2 in ESCC tissues was often associated with high expression of ki67 and p53(P<0.05).ConclusionMTHFD2 had significantly enhanced expression in ESCC tissues and was associated with pathological grading and TNM stage.Taken together,high expression of MTHFD2 was an independent unfavorable prognostic parameter for overall survival(OS)of ESCC patients,suggesting that MTHFD2 might be a potential therapeutic target for ESCC in the future.