Abstract
Background
Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown.
Methods
Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis.
Results
The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cells、Macrophages M2、CD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers.
Conclusions
We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
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Data availability
The data sets analyzed during the current study are available in the UCSC Xena database (http://xena.ucsc.edu/), CPTAC database (https://pdc.cancer.gov/pdc/), Human Protein Atlas database (http://www.proteinatlas.org/), CellMiner database (https://discover.nci.nih.gov/cellminer/home.do), and RCSB PDB database (https://www.rcsb.org/). Other data may be obtained from the corresponding author upon reasonable request.
Abbreviations
- ACC:
-
Adrenocortical carcinoma
- BLCA:
-
Bladder urothelial carcinoma
- BRCA:
-
Breast carcinoma
- CESC:
-
Cervical squamous cell carcinoma and endocervical adenocarcinoma
- CHOL:
-
Cholangiocarcinoma
- CI:
-
Confidence interval
- COAD:
-
Colon adenocarcinoma
- CPTAC:
-
Clinical Proteomic Tumor Analysis Consortium
- DFI:
-
Disease-free interval
- DLBC:
-
Lymphoid neoplasm diffuse large B-cell lymphoma
- DSS:
-
Disease-specific survival
- ESCA:
-
Esophageal carcinoma
- GBM:
-
Glioblastoma multiforme
- GSEA:
-
Gene Set Enrichment Analysis
- GTEx:
-
Genote-Tissue Expression
- HNSC:
-
Head and neck squamous cell carcinoma
- HPA:
-
Human Protein Atlas
- HR:
-
Hazard ratio
- IC50:
-
Half maximal inhibitory concentration
- ICIs:
-
Immune checkpoint inhibitors
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- KICH:
-
Kidney chromophobe
- KIRC:
-
Kidney renal clear cell carcinoma
- KIRP:
-
Kidney renal papillary cell carcinoma
- LAML:
-
Acute myeloid leukemia
- LGG:
-
Brain lower grade glioma
- LIHC:
-
Liver hepatocellular carcinoma
- LUAD:
-
Lung adenocarcinoma
- LUSC:
-
Lung squamous cell carcinoma
- MESO:
-
Mesothelioma
- MSI:
-
Microsatellite instability
- NK:
-
Natural killer
- OS:
-
Overall survival
- OV:
-
Ovarian serous cystadenocarcinoma
- PAAD:
-
Pancreatic adenocarcinoma
- PCPG:
-
Pheochromocytoma and paraganglioma
- PDB:
-
Protein Data Bank
- PFI:
-
Progression-free interval
- PRAD:
-
Prostate adenocarcinoma
- READ:
-
Rectum adenocarcinoma
- SARC:
-
Sarcoma
- SKCM:
-
Skin cutaneous melanoma
- STAD:
-
Stomach adenocarcinoma
- TCA:
-
Tricarboxylic acid
- TCGA:
-
The Carcinoma Genome Atlas
- TGCT:
-
Testicular germ cell tumors
- THCA:
-
Thyroid carcinoma
- THYM:
-
Thymoma
- TIDE:
-
Tumor immune dysfunction and exclusion
- TMB:
-
Tumor mutational burden
- TME:
-
Tumor microenvironment
- UCEC:
-
Uterine corpus endometrial carcinoma
- UCS:
-
Uterine carcinosarcoma
- UVM:
-
Uveal melanomas
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Funding
This work was supported by the National Natural Science Foundation of China (82373155, 82103293, 82172651), the Natural Science Foundation of Anhui Province (2108085MH287), the Natural Science Foundation of Anhui Education Department for Distinguished Young Scholars (2022AH020074), the Natural Science Foundation of Anhui Education Department for Excellent Young Scholars (2022AH030123), the Support Plan for Outstanding Young Talents of Anhui Education Department (gxyq2021257), the Key Research and Development Project of Anhui Province (202104j07020019), the Science and Technology Project of Wuhu City (2022jc52) and the Talent Introduction Science Foundation of Yijishan Hospital, Wannan Medical College (No. YR202109 and YR202110).
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YF: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, writing—original draft preparation, writing—review and editing. DC: conceptualization, data curation, formal analysis, methodology, validation, visualization, writing—original draft preparation, writing—review and editing. RD: methodology, software, validation. YL: data curation, investigation, supervision, validation. ZW: investigation, supervision, visualization. PG: software, supervision, visualization. MZ: software, supervision, visualization. XW: supervision, writing—review and editing. XZ: conceptualization, data curation, methodology, resources, validation, writing—review and editing, funding acquisition. JC: conceptualization, project administration, resources, validation, funding acquisition.
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Fei, Y., Cao, D., Dong, R. et al. The cuproptosis-related gene UBE2D2 functions as an immunotherapeutic and prognostic biomarker in pan-cancer. Clin Transl Oncol (2024). https://doi.org/10.1007/s12094-024-03495-4
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DOI: https://doi.org/10.1007/s12094-024-03495-4