Prognostic value of ubiquitin E2 UBE2W and its correlation with tumor-infiltrating immune cells in breast cancer

Abstract

Background: Ubiquitin-conjugating enzyme E2W (UBE2W) is a protein-coding gene that has an important role in ubiquitination and may be vital in the repair of DNA damage. However, studies on the prognostic value of UBE2W and its correlation with tumor-infiltrating immune cells in multiple cancers have not been addressed.

Methods: We investigated UBE2W expression in the Oncomine database, the Tumor Immune Estimation Resource (TIMER), TNMplot database. Then, the clinical prognostic value of UBE2W was analyzed via online public databases. Meanwhile, we explored the correlation between UBE2W and DNA repair associate genes expression and DNA methyltransferase expression by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). By using the same method, the correlation between UBE2W and tumor-infiltrating immune cells was explored. Genomic Profiles of UBE2W in breast cancer (BRCA) were accessed in cBioPortal (v3.5.0). Functional proteins associated network was analyzed by STRING database (v11.0).

Results: UBE2W was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels, DNA methyltransferase, and BRCA1/2 expression in breast cancer. High expression of UBE2W may promote the tumor immunosuppression and metastasis, induce endocrine therapy resistance and deteriorate outcomes of patients with breast cancer. These findings suggest that UBE2W could be a potential biomarker of prognosis and tumor-infiltrating immune cells. Besides, RBX1 may be a new E3 that was regulated by UBE2W.

Conclusions: Ubiquitin E2 UBE2W is a potential prognostic biomarker and is correlated with immune infiltration in BRCA.

Keywords: Breast cancer; Endocrine therapy resistance; Prognosis; Tumor immune environment; UBE2W.

Fig. 1

Expression of UBE2W in various human tumors. a Increased expression of UBE2W in different tumors compared to normal tissues in the Oncomine database. b UBE2W expression of different tumor types from the TCGA database was investigated by TIMER (*P < 0.05, **P < 0.01, ***P < 0.001). c UBE2W was abnormally expressed in pan cancers by TNMplot. Significant differences by Mann-Whitney U test are marked with red color. Abbreviations: ACC: adrenocortical carcinoma; BLCA: bladder urothelial carcinoma; BRCA: breast invasive carcinoma; CESC: cervical squamous cell carcinoma; CHOL: cholangiocarcinoma; COAD: colon adenocarcinoma; DLBC: lymphoid neoplasm diffuse large B cell lymphoma; ESCA: esophageal carcinoma; GBM: glioblastoma multiforme; LGG: brain lower grade glioma; HNSC: head and neck squamous cell carcinoma; KICH: kidney chromophobe; KIRC: kidney renal clear cell carcinoma; KIRP: kidney renal papillary cell carcinoma; LAML: acute myeloid leukemia; LIHC: liver hepatocellular carcinoma; LUAD: lung adenocarcinoma; LUSC: lung squamous cell carcinoma; MESO: mesothelioma; OV: ovarian serous cystadenocarcinoma; PAAD: pancreatic adenocarcinoma; PCPG: pheochromocytoma and paraganglioma; PRAD: prostate adenocarcinoma; READ: rectum adenocarcinoma; SARC: sarcoma; SKCM: skin cutaneous melanoma; STAD: stomach adenocarcinoma; TGCT: testicular germ cell tumors; THCA: thyroid carcinoma; THYM: thymoma; UCEC: uterine corpus endometrial carcinoma; UCS: uterine carcinosarcoma; and UVM: uveal melanoma; AML: ; Lung_AC: lung adenocarcinoma; Lung_SC: lung squamous cell carcinoma; Renal_CC: renal clear cell carcinoma; Renal_CH: renal chromophobe cell carcinoma; Renal_PA: renal papillary cell carcinoma; Uterus_CS: uterine carcinosarcoma; Uterus_EC: uterine corpus endometrial carcinoma

Fig. 2

Survival analysis and predictive value analysis of UBE2W in public databases. a-c Overall survival (OS), Relapse free survival (RFS), and Distant metastasis-free survival curves of BRCA by different expression levels of UBE2W in the K-M plotter database. d-e OS and RFS curves of BRCA by different expression levels of UBE2W in the PrognoScan database. f Gene chip data of UBE2W expression in normal, tumor, metastatic tissues. g RNA-seq data of UBE2W expression in normal, tumor, metastatic tissues. h UBE2W expression between responders and non-responders in endocrine therapy of BRCA. i The ROC plot of UBE2W expression in predicting the effect of endocrine therapy in BRCA. Abbreviations: OS: overall survival; RFS: relapse-free survival; DMFS: distant metastasis free survival

Fig. 3

Correlation of UBE2W expression with DNA repair and DNA methyltransferase genes in BRCA

Fig. 4

Correlation of UBE2W expression with immune infiltration level in BRCA

Fig. 5

Genomic alterations of UBE2W of BRCA in cBioPortal. a Oncoprint of UBE2W alteration in BRCA. b Mutation details for UBE2W. c, d Survival analysis. Abbreviations: OS: overall survival