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Article Open Access

UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses

  • Authors:
    • Yun Wen
    • Pengfei Luo
  • View Affiliations / Copyright

    Affiliations: Department of Breast and Thyroid Surgery, The Central Hospital of Yongzhou, Yongzhou, Hunan 425000, P.R. China, Department of Oncology, The Central Hospital of Yongzhou, Yongzhou, Hunan 425000, P.R. China
    Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 260
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    Published online on: July 23, 2026
       https://doi.org/10.3892/mmr.2026.13970
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Abstract

Ubiquitin‑conjugating enzyme E2A (UBE2A), a member of the ubiquitin‑conjugating E2 enzyme family, has been implicated in tumor development; however, its role across human cancer types remains incompletely understood. The present study aimed to systematically characterize the expression pattern, prognostic importance and immune relevance of UBE2A in a pan‑cancer context. Public datasets, including The Cancer Genome Atlas, Gene Expression Omnibus and Genotype‑Tissue Expression, were integrated to evaluate UBE2A expression, clinical importance, molecular characteristics, immune associations and biological functions across cancer types. Single‑cell RNA sequencing data were analyzed to investigate the cellular distribution of UBE2A. Functional validation was performed through UBE2A knockdown in breast cancer cell lines. Results indicated that UBE2A was significantly upregulated in a number of cancer types and was associated with unfavorable overall and progression‑free survival. UBE2A expression exhibited significant correlations with immune cell infiltration and immune checkpoint‑associated genes across cancer types. Functional enrichment analyses indicated that UBE2A was primarily involved in cell cycle regulation and proliferative processes. Single‑cell analysis revealed preferential UBE2A expression in proliferative T‑cell populations. Furthermore, in vitro experiments demonstrated that UBE2A knockdown significantly suppressed breast cancer cell proliferation, migration and invasion. Overall, UBE2A was shown to be a promising prognostic biomarker associated with tumor progression, cell cycle activity and immune‑associated characteristics across cancer types. Its preferential expression in proliferative T‑cell populations and oncogenic role in breast cancer suggest that UBE2A may serve as a potential therapeutic target and a candidate biomarker for evaluating tumor prognosis and the tumor immune microenvironment.
View Figures

Figure 1

Study overview. An integrated
pan-cancer analysis based on The Cancer Genome Atlas datasets was
performed to systematically characterize the expression patterns,
prognostic value, epigenetic regulation and immune relevance of
UBE2A. In vitro functional assays in breast cancer cell
lines further validated the oncogenic role of UBE2A in cancer
progression. The graphical abstract was created using BioRender.
UBE2A, ubiquitin conjugating enzyme E2A; qPCR, quantitative PCR;
CCK-8; Cell Counting Kit-8.

Figure 2

Expression landscape of UBE2A across
human cancers. (A) Differential expression analysis of UBE2A
between tumor and normal tissues across TCGA cancer types. (B)
UBE2A expression profiles based on integrated TCGA and
Genotype-Tissue Expression Project datasets. (C) Paired comparison
of UBE2A expression between tumor tissues and matched adjacent
normal tissues in TCGA cohorts. (D) Independent validation of UBE2A
expression in the breast cancer cohort GSE29044. (E) Independent
validation of UBE2A expression in the breast cancer cohort
GSE65194. *P<0.05, **P<0.01, ***P<0.001 and
****P<0.0001. UBE2A, ubiquitin conjugating enzyme E2A; TCGA, The
Cancer Genome Atlas; TPM, transcripts per million; ns, not
significant.

Figure 3

Associations between UBE2A expression
and clinicopathological parameters in pan-cancer analysis. (A)
Distribution of UBE2A expression across different T stages in
selected cancer types. (B) Association between UBE2A expression and
N stage across cancer types. (C) UBE2A expression according to
integrated TNM stage in pan-cancer cohorts. *P<0.05,
**P<0.01, ***P<0.001 and ****P<0.0001. UBE2A, ubiquitin
conjugating enzyme E2A.

Figure 4

Diagnostic performance of UBE2A
expression across cancer types. Receiver operating characteristic
(ROC) curves evaluating the ability of UBE2A expression to
distinguish tumor tissues from normal tissues in (A) BLCA, (B)
BRCA, (C) CESC, (D) CHOL, (E) ESAD, (F) ESCA, (G) GBM, (H) HNSC,
(I) KICH, (J) LIHC, (K) LUAD, (L) LUSC, (M) OSCC, (N) PCPG and (O)
STAD. UBE2A, ubiquitin conjugating enzyme E2A; ROC, receiver
operating characteristic; AUC, area under the curve; FPR, false
positive rate; TRP, true positive rate.

Figure 5

Prognostic relevance of UBE2A
expression across human cancers. (A) Overview of the associations
between UBE2A expression and OS across TCGA cancer types.
Kaplan-Meier analysis of OS in (B) BRCA, (C) LGG, (D) LIHC, (E)
MESO, (F) SARC and (G) UVM. (H) Overview of the associations
between UBE2A expression and DFS across TCGA cancer types.
Kaplan-Meier analysis of DFS in (I) LGG, (J) LIHC and (K) UVM. (L)
Kaplan-Meier Plotter validation of OS in BRCA. (M) Kaplan-Meier
Plotter validation of RFS in BRCA. (N) Kaplan-Meier Plotter
validation of DMFS in BRCA. UBE2A, ubiquitin conjugating enzyme
E2A; OS, overall survival; DFS, disease-free survival; RFS,
relapse-free survival; HR, hazard ratio.

Figure 6

Genomic landscape of UBE2A
aberrations across cancer types. (A) Overall mutation frequency of
UBE2A across all cancer types. (B) Frequency of UBE2A alterations
across different tumor types. (C) Mutation site distribution in
UBE2A. (D) Classification of UBE2A alteration types. (E)
Co-mutation analysis of UBE2A and associated genes. UBE2A,
ubiquitin conjugating enzyme E2A; CNA, copy number alteration;
RSEM, RNA-Seq by expectation-maximization; VUS, variant of
uncertain significance; GISTIC, genomic identification of
significant targets in cancer.

Figure 7

Co-expression analysis, functional
enrichment and PPI network of UBE2A. Heatmaps showing the top 50
genes positively (A) and negatively (B) correlated with UBE2A
expression. (C) GO enrichment analysis of UBE2A co-expressed genes.
(D) KEGG pathway enrichment analysis of UBE2A-associated gene sets.
(E) Gene Set Enrichment Analysis comparing high and low UBE2A
expression groups in the BRCA cohort. (F) PPI network of UBE2A
generated using GeneMANIA. UBE2A, ubiquitin conjugating enzyme E2A;
PPI, protein-protein interaction; GO, Gene Ontology; GOBP, GO
biological process; GOMF, GO molecular function; KEGG, Kyoto
Encyclopedia of Genes and Genomes.

Figure 8

DNA promoter methylation and mRNA
methylation analysis of UBE2A across human cancers. Promoter
methylation levels of UBE2A in (A) BLCA, (B) LIHC, (C) BRCA, (D)
STAD and (E) PRAD from the University of Alabama at Birmingham
Cancer Data Analysis Portal database. (F) Correlation between UBE2A
expression and RNA methylation-associated genes across cancers.
*P<0.05. UBE2A, ubiquitin conjugating enzyme E2A; TCGA, The
Cancer Genome Atlas.

Figure 9

UBE2A expression patterns across
molecular and immune subtypes in 33 cancer types. (A-H) UBE2A
expression among molecular subtypes in (A) BRCA, (B) COAD, (C)
HNSC, (D) KIRP, (E) LGG and (F) LUSC, (G) OV and (H) PCPG. (I-T)
UBE2A expression profiles across immune subtypes in (I) BLBA, (J)
BRCA, (K) ESCA, (L) KIRC, (M) KIRP, (N) LGG, (O) LUAD, (P) LUSC,
(Q) OV, (R) PAAD, (S) STAD and (T) UCEC. UBE2A, ubiquitin
conjugating enzyme E2A; Lum, luminal; CIN, chromosomal instability;
GS, genomically stable; HM, hypermutated; SNV, single nucleotide
variant; indel, insertion/deletion; G-CIMP, glioma CpG island
methylator phenotype.

Figure 10

Associations of UBE2A expression with
the immune microenvironment, TMB and MSI across cancers. (A)
Heatmap showing the correlation between UBE2A expression and
infiltration levels of 22 immune cell types across various cancers.
(B) Correlation analysis between UBE2A expression and TMB in
pan-cancer. (C) Correlation between UBE2A expression and MSI across
cancers. *P<0.05, **P<0.01 and ***P<0.001. UBE2A,
ubiquitin conjugating enzyme E2A; TMB, tumor mutational burden;
MSI, microsatellite instability.

Figure 11

Single-cell transcriptomic
characterization of UBE2A expression in breast cancer. Uniform
Manifold Approximation and Projection and Violin plots showing the
expression levels of UBE2A across different cellular subpopulations
in BRCA single-cell RNA sequencing datasets (A) GSE114727, (B)
GSE110686, (C) GSE148673 and (D) GSE176078. (E) UBE2A expression
landscape across cellular subpopulations, highlighting preferential
expression in proliferative T-cell populations. UBE2A, ubiquitin
conjugating enzyme E2A; TPM, transcripts per million; DC, dendritic
cell; SMC, smooth muscle cell; conv, conventional T cell; ex,
exhausted T cell; Tprolif, proliferative T-cell; Treg, regulatory
T-cell.

Figure 12

UBE2A expression in BRCA cell lines
and validation of siRNA-mediated knockdown. (A) Relative UBE2A mRNA
levels in BRCA cell lines and the normal breast epithelial cell
line determined by qPCR. (B) qPCR analysis of UBE2A mRNA levels
following transfection with three siRNAs in MDA-MB-231 cells. (C)
qPCR analysis of UBE2A mRNA levels following transfection with
three siRNAs in MCF-7 cells. (D-G) Western blotting assessment of
UBE2A protein expression after siRNA transfection. (H and I) Cell
Counting Kit-8 assays evaluating the effects of UBE2A knockdown on
proliferation in MDA-MB-231 and MCF-7 cells. Statistical
comparisons were performed relative to the siNC group. *P<0.05,
**P<0.01, ***P<0.001 and ****P<0.0001. UBE2A, ubiquitin
conjugating enzyme E2A; si, small interfering; NC, negative
control; qPCR, quantitative PCR; OD450, optical density at 450 nm;
ns, not significant.

Figure 13

Effects of UBE2A knockdown on
migration and invasion of BRCA cells. (A) Representative wound
healing images of MDA-MB-231 cells following UBE2A knockdown.
Magnification, ×4. (B) Quantitative analysis of wound closure in
MDA-MB-231 cells. (C) Representative wound healing images of MCF-7
cells following UBE2A knockdown. Magnification, ×4. (D)
Quantitative analysis of wound closure in MCF-7 cells. (E)
Representative images of Transwell migration and invasion assays in
MDA-MB-231 cells. Magnification, ×10. (F) Quantification of
migrated MDA-MB-231 cells. (G) Quantification of invaded MDA-MB-231
cells. (H) Representative images of Transwell migration and
invasion assays in MCF-7 cells. Magnification, ×10. (I)
Quantification of migrated MCF-7 cells. (J) Quantification of
invaded MCF-7 cells. Statistical comparisons were performed
relative to the siNC group. Statistical comparisons were performed
relative to the siNC group. **P<0.01, ***P<0.001 and
****P<0.0001. UBE2A, ubiquitin conjugating enzyme E2A; si, small
interfering; NC, negative control.
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Copy and paste a formatted citation
Spandidos Publications style
Wen Y and Luo P: UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses. Mol Med Rep 34: 260, 2026.
APA
Wen, Y., & Luo, P. (2026). UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses. Molecular Medicine Reports, 34, 260. https://doi.org/10.3892/mmr.2026.13970
MLA
Wen, Y., Luo, P."UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses". Molecular Medicine Reports 34.4 (2026): 260.
Chicago
Wen, Y., Luo, P."UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses". Molecular Medicine Reports 34, no. 4 (2026): 260. https://doi.org/10.3892/mmr.2026.13970
Copy and paste a formatted citation
x
Spandidos Publications style
Wen Y and Luo P: UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses. Mol Med Rep 34: 260, 2026.
APA
Wen, Y., & Luo, P. (2026). UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses. Molecular Medicine Reports, 34, 260. https://doi.org/10.3892/mmr.2026.13970
MLA
Wen, Y., Luo, P."UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses". Molecular Medicine Reports 34.4 (2026): 260.
Chicago
Wen, Y., Luo, P."UBE2A as a prognostic indicator across human cancers: Insights from multi‑omics and immune landscape analyses". Molecular Medicine Reports 34, no. 4 (2026): 260. https://doi.org/10.3892/mmr.2026.13970
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