| Objective The purpose of this study is to search for potential therapeutic target genes of esophageal squamous cell carcinoma and explore the possibility of using them as prognostic markers for patients with esophageal squamous cell carcinoma.Methods The hub genes were screened from esophageal squamous cell carcinoma and paracancerous tissues by bioinformatics analysis,and then verified by tissue RNA extraction and RT-qRCR.Mann-Whitney U nonparametric test and Kaplan-Meier survival analysis were used to study the correlation between the relative expression of differentially expressed genes and the clinicopathology and prognosis of patients with esophageal squamous cell carcinoma,and subgroup analysis was performed.Cox proportional hazards model and Kaplan-Meier were used to analyze the factors affecting the prognosis of patients with esophageal squamous cell carcinoma.Results GEO2R detected 279 differentially expressed genes in esophageal squamous cell carcinoma/paracancerous tissues.Cluster analysis and enrichment analysis showed that Cluster 4 played an important role in immune-related functions.PPI network showed that IFIT3 was the hub gene in the gene cluster.IFIT3(Interferoninduced protein with transcribed repeats 3),as one of the important genes in response to interferon stimulation,plays an important role in the antiviral and anti-tumor processes.The differential expression of IFIT3 in cancer/paracancerous tissues was verified by qPCR of clinical patient tissue samples(P<0.05).Mann-Whitney U test results of independent samples showed that the expression of IFIT3 was significantly correlated with the maximum diameter of the tumor,the degree of tumor differentiation,neoadjuvant immunotherapy,lymph node metastasis,distant metastasis,and TNM stage in patients with esophageal squamous cell carcinoma(P<0.05).Kaplan-Meier analysis showed that the disease-free survival time and total survival time of patients with low expression of IFIT3 were significantly higher than those of patients with high expression of IFIT3.The results were significant in subgroups of age<60,male,G1-2 differentiation,middle esophagus,ulcerative type,without neoadjuvant immunotherapy,NO stage,M0 stage,TNM Ⅰ-Ⅱ stage,maximum tumor diameter≥ 4 cm(all P<0.05).Kaplan-Meier analysis and Cox proportional hazards model showed that the prognosis of patients with female,high and middle differentiation,maximum tumor diameter<4cm T1-2 stage,no lymph node metastasis,no distant metastasis,and TNM Ⅰ-Ⅱ stage was better(P<0.05);Male,tumor diameter ≥ 4cm,T3-4 stage,lymph node metastasis,distant metastasis,TNM Ⅲ-Ⅳ stage,and IFIT3 high expression are all prognostic risk factors,and lymph node metastasis is an independent risk factor affecting the prognosis of patients with esophageal squamous cell carcinoma(all HR>1,P<0.05).Conclusion Research shows that IFIT3 is a differentially expressed gene between esophageal squamous cell carcinoma and paracancerous tissues,and the relative expression level is related to clinical pathology and prognosis,suggesting that IFIT3 plays an important role in the occurrence and development of esophageal squamous cell carcinoma,and can be used as an important indicator to judge the poor prognosis of patients with esophageal squamous cell carcinoma. |
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