Combined Evaluation of mRNA and Protein Expression, Promoter Methylation, and Immune Infiltration of UBE2I in Pan-Digestive System Tumors

Abstract

Background: Digestive system tumors (DSTs) have high morbidity and mortality worldwide. This study explored the potential value of ubiquitin-conjugating enzyme E2 I (UBE2I) in pan-digestive system tumors (pan-DSTs).

Methods: Differential expression, tumor stages, and survival outcomes of UBE2I in pan-DSTs were determined using the GEPIA database. The TIMER database was used to confirm the correlation of UBE2I expression with pan-DSTs and immune infiltrates. Differential analyses of UBE2I promoter methylation and protein levels were performed using the UALCAN database. The underlying mechanisms of UBE2I involvement in pan-DSTs were visualized using interaction networks. The diagnostic value of UBE2I in pan-DSTs was identified using the Oncomine database.

Results: UBE2I was differentially and highly expressed in cholangiocarcinoma (CHOL), pancreatic adenocarcinoma (PAAD), colon adenocarcinoma (COAD), rectal adenocarcinoma (READ), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD). According to survival analysis, upregulated UBE2I was associated with adverse overall and disease-free survival in PAAD and favorable overall survival in READ. UBE2I expression was partially linked to the purity of immune infiltration in COAD, LIHC, PAAD, READ, and STAD, as indicated by the immune infiltration analysis. Promoter methylation analysis showed differential and high methylation of UBE2I in PAAD as well as stratified analysis by gender, nodal metastasis, and race. Protein expression analysis in colon cancer revealed that UBE2I had differential and high expression in tumors as well as stratified analysis by gender, tumor histology, race, and tumor stage. Mechanism explorations demonstrated that in COAD and PAAD, UBE2I was involved in spliceosomal snRNP complex, Notch signaling pathway, etc. Diagnostic analysis indicated that UBE2I had consistent diagnostic value for COAD and PAAD.

Conclusions: Upregulated UBE2I may be a diagnostic and surveillance predictive signature for PAAD and COAD. The potential significance of immune infiltrates and promoter methylation in PAAD and COAD needs further exploration.

Figure 1

Differentialexpression and disease progression plots of UBE2I in pan-DSTs. (a) Differential expression patterns of UBE2I in pan-DSTs from TCGA. (b) Differential expression patterns of UBE2I in pan-DSTs. (c–i) Disease progression plots between UBE2I expression and tumor stage in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 2

Overall and disease-free survival plots in relation to UBE2I expression in pan-DSTs. (a–g) Overall survival plots based on UBE2I expression in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD. (h–n) Disease-free survival plots based on UBE2I expression in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 3

Correlation analysis of UBE2I expression with immune infiltrates. (a–g) Correlations of UBE2I with immune infiltrates (purity, B cells, CD8⁺ T cells, CD4⁺ T cells, MP, NP, and DC) in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 4

Analysis of associations between SCNAs of UBE2I and immune infiltrates of pan-DSTs. (a–g) Analysis of the correlation of SCNAs of UBE2I with immune infiltrates (B cells, CD8⁺ T cells, CD4⁺ T cells, MP NP, and DC) in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 5

Immune infiltrate-related survival and UBE2I expression in pan-DSTs. (a–g) Immune infiltrate-related survival and UBE2I expression in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 6

Promoter methylation analysis of UBE2I in pan-DSTs and stratified analyses by gender, lymph node, and race. (a–g) Promoter methylation analysis of UBE2I in pan-DSTs and stratified analyses by gender, lymph node, and race in CHOL, COAD, ESCA, LIHC, PAAD, READ, and STAD.

Figure 7

Protein expression analysis of UBE2I in tumors. (a–e) Stratified analyses by gender, race, tumor stage, and tumor histology in colon cancer.

Figure 8

Illustration of functional enrichment pathways of UBE2I and coexpressed genes involved in COAD.

Figure 9

Illustration of interaction networks of UBE2I and coexpressed genes involved in PAAD.

Figure 10

Gene-gene and protein-protein interaction networks. (a) Gene-gene interaction networks of UBE2I and related genes. (b) Protein-protein interaction networks of UBE2I and related proteins.

Figure 11

Differential expression and diagnostic ROC curves of UBE2I in COAD and PAAD. (a, c) Differential expression of UBE2I in COAD. (b, d) Diagnostic ROC curve of UBE2I in COAD. (e, g) Differential expression of UBE2I in PAAD. (f, h) Diagnostic ROC curve of UBE2I in PAAD.