Abstract

Background: The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. However, no publication has reported its implication in esophageal squamous cell cancer (ESCC). Methods: We explored several public databases, including The Cancer Genome Atlas (TCGA), Oncomine, and gene expression Omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and gene set enrichment analysis (GSEA) were adopted to explore involved signaling pathways. We used R software to develop prognostic gene signatures with the LASSO and stepwise Cox regression analysis, separately. Immunohistochemistry staining was performed to detect UBE2T in 90 ESCC patients, followed by survival analysis. We also used an R package pRRophetic to evaluate chemotherapy sensitivity for the TCGA–ESCC cohort. Results: We found significantly increased UBE2T transcript levels and DNA copy numbers in ESCC tissues. UBE2T was associated with the p53 signaling pathway, cell cycle, Fanconi anemia pathway, and DNA replication, as indicated by Go, KEGG pathway enrichment analysis. These pathways were also upregulated in ESCC. The prognostic signatures with UBE2T-associated genes could stratify ESCC patients into low- and high-risk groups with significantly different overall survival in the TCGA–ESCC cohort. We also validated the association of UBE2T with unfavorable survival in 90 ESCC patients recruited for this study. Moreover, we found that the low-risk group was significantly more sensitive to chemotherapy than the high-risk group. Conclusions: UBE2T is involved in the development of ESCC, and gene signatures derived from UBE2T-associated genes are predictive of prognosis in ESCC.

Highlights

  • Esophageal cancer (EC) is one of the major health problems, which ranks 7th for incidence (572,000 new cases), but 6th for mortality (509,000 deaths) worldwide [1]

  • We first compared the expression of ubiquitin-conjugating enzyme E2 T (UBE2T) in esophageal cancer and normal tissues by mining the Oncomine database

  • The mRNA expression levels of UBE2T in esophageal squamous cell cancer (ESCC) were significantly enhanced in one study by Su et al [17]

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Summary

Introduction

Esophageal cancer (EC) is one of the major health problems, which ranks 7th for incidence (572,000 new cases), but 6th for mortality (509,000 deaths) worldwide [1]. EC is mainly composed of esophageal squamous cell cancer (ESCC) and adenocarcinoma. UBE2T Contributes to ESCC Prognosis accounting for over 90% of all EC cases [1, 2]. Half of the EC patients present with unresectable or metastatic lesions at the time of diagnosis. Understanding the molecular mechanisms of ESCC may accelerate novel therapy development and the discovery of biomarkers for early diagnosis and prognosis. The ubiquitin-conjugating enzyme E2 T (UBE2T) has been shown to contribute to several types of cancer. No publication has reported its implication in esophageal squamous cell cancer (ESCC)

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