Pan-Cancer Analyses of the Tumor Microenvironment Reveal That Ubiquitin-Conjugating Enzyme E2C Might Be a Potential Immunotherapy Target

Abstract

Increasing evidence indicated that the tumor microenvironment (TME) played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C (UBE2C) was differentially expressed in many cancer types. However, the immunological and prognostic roles of UBE2C were unclear. Differentially expressed genes (DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types failed to download owing to no DEGs. Furthermore, the gene expression profiles, mutation data, and survival data of 33 cancer types were obtained from UCSC Xena. Clinical stage relevance, tumor mutational burden (TMB), TME relevance analysis, and gene set enrichment analysis (GSEA) of DEGs in 33 cancer types were performed. And DEGs were identified in oral squamous cell carcinoma (OSCC) by biological experiments. Previous studies indicated that UBE2C was related to the prognosis of many cancers. In our study, the higher UBE2C expression level meant a terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. In addition, both immune relevance analysis and GSEA showed that UBE2C might participate in immune response in many cancers. Furthermore, the UBE2C mRNA level and protein level were all identified as upregulated in OSCC cell lines and tissues. UBE2C was differentially expressed in many cancer types and related to the pathogenesis and TME of many cancers, which might be a potential diagnostic and therapeutic biomarker.

UBE2C: A pan‐cancer diagnostic and prognostic biomarker revealed through bioinformatics analysis

“…50 UBE2C expression has been found to be positively associated with immune checkpoint-related genes, including CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, SIGLEC15, and TIGIT in various cancers. 40,51 Moreover, most of the immune-related markers and metabolism-related pathways were associated with UBE2C expression level in THCA. 50 In hepatocellular carcinoma, UBE2C was found to be positively correlated with the infiltration of regulatory T cells and T follicular helper cells.…”

“…Moreover, studies have highlighted the significance of TMB (tumor mutational burden) as a novel biomarker predicting immunotherapeutic response and its association with prognosis in 13 different cancer types. 51 Variations in prognosis among cancers may be attributed to tumor heterogeneity.…”

“…Acting as an oncogene in these cancers, UBE2C plays a crucial role in both cancer development and therapy, suggesting its potential as an effective therapeutic target for pan‐cancer. Moreover, studies have highlighted the significance of TMB (tumor mutational burden) as a novel biomarker predicting immunotherapeutic response and its association with prognosis in 13 different cancer types 51 . Variations in prognosis among cancers may be attributed to tumor heterogeneity.…”

“…Furthermore, UBE2C has been identified as a potential diagnostic and therapeutic biomarker, as well as a prognostic signature for various cancers. The overexpression of UBE2C has been associated with tumor progression 51,56 and poor prognosis in different cancer types, making it a potential target for immunotherapy. The role of UBE2C in the aggressive progression of various cancers, including tongue squamous cell carcinoma, renal cell carcinoma, thyroid carcinoma, and glioma, has been well‐documented 50 .…”

Diverse roles of UBE2T in cancer (Review)

“…Increasing evidence has verified that E2s show dysregulation in various cancer types, as they are linked to tumor-promoting processes and self-renewal abilities such as dysregulation in DNA repair, cell cycle, apoptosis and oncogenic signalling (10,(17)(18)(19)(20)(21)(22). The dysfunctional status of E2 members is considered a potential biomarker for diagnosis, prognosis and therapy in patients with various cancer types (22)(23)(24)(25)(26)(27)(28)(29)(30)(31).…”