The investigation of the potential application values of UCHL3 high expression level as a prognostic marker of esophageal cancer based on bioinformatics analysis

LIU Pingli; ZHANG Li

doi:10.3969/j.issn.1674-4136.2025.03.011

Abstract：Objective To investigate the potential values of high expression level of ubiquitin C-terminal hydrolase L3(UCHL3)as a prognostic marker of esophageal cancer(EC)based on bioinformatics analysis.Methods Based on the original data from the public database,the expression of UCHL3 gene in esophageal cancer was detected,the expression of UCHL3 protein was detected by HPA,Kruskal-Wallis test was used to analyze the correlation between UCHL3 and the clinical and pathological stages of EC,the survival time of patients was analyzed by Kaplan-Meier.The correlation between UCHL3 and immune infiltration matrix data was analyzed by ssGSEA algorithm.LinkedOmics analyzed the enrichment of UCHL3 gene,and GSEA analyzed the signaling pathway of UCHL3.Results In pan-cancer analysis,compared with normal tissues,UCHL3 mRNA expression levels were elevated in 18 of 33 cancers(P＜0.05).High expression levels of UCHL3 was significantly associated with poor prognosis of THCA(thyroid cancer)and EC(esophageal cancer)(P＜0.05).Immunohistochemical staining showed that compared with adjacent normal tissues,UCHL3 protein expression was up-regulated in EC tissues(P＜0.05).UCHL3 expression was significantly correlated with pathological stage,clinical stage and lymph node metastasis(P＜0.05).The sensitivity and specificity of UCHL3 expression level as a predictor for 1-year and 3-year prognosis(OS,DSS,and PFS)in EC patients was good.UCHL3 high expression level was associated with poor prognosis in EC patients.In the pathological stageⅠ-Ⅱ and TNM stage T1T2N0N1M0 groups,compared with EC patients with lower UCHL3 expression level,the EC patients with higher UCHL3 expression level had significantly worse OS.The GO analysis of UCHL3 showed that the biological processes mainly included visual development,metal ion response,signal release and lymphocyte differentiation,et al.The molecular function of UCHL3 mainly included the activity of protein tyrosine kinase and anion transmembrane transporter,et al.The KEGG pathway analysis of UCHL3 showed that the liver cancer signaling pathway and thyroid hormone signaling pathway were significantly related.According to the differentially expresses genes(DEGs)and the gene set enrichment pathway analysis between the two gene sets of low expression group and high expression group of UCHL3,UCHL3 is mainly involved in angiogenesis,IL-6-JAK-STAT3 signaling pathway,bile acid metabolism,coagulation pathway,Notch signaling pathway,Hedgehog signaling pathway,reactive oxygen species signaling pathway and peroxisome signaling pathway,et al.Conclusions The high expression level of UCHL3 has the potential application value as a prognostic marker of EC.