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Published on: October 10, 2022
Identification and validation of a novel ubiquitination-related gene UBE2T in Ewing's sarcoma
Guoxin Qu1,2,3, Yuanchun Xu3,4, Ye Qu4
1Department of Orthopaedics, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, China.
Background:
Ewing's sarcoma (ES) is one of the most prevalent malignant bone tumors worldwide. However, the molecular mechanisms of the genes and signaling pathways of ES are still not well sufficiently comprehended. To identify candidate genes involved in the development and progression of ES, the study screened for key genes and biological pathways related to ES using bioinformatics methods.
Methods:
The GSE45544 and GSE17618 microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, and functional enrichment analysis was performed. A protein-protein interaction (PPI) network was built, and key module analysis was performed using STRING and Cytoscape. A core-gene was gained and was validated by the validation dataset GSE67886 and immunohistochemistry (IHC). The diagnostic value and prognosis evaluation of ES were executed using, respectively, the ROC approach and Cox Regression.
Results:
A total of 187 DEGs, consisting of 56 downregulated genes and 131 upregulated genes, were identified by comparing the tumor samples to normal samples. The enriched functions and pathways of the DEGs, including cell division, mitotic nuclear division, cell proliferation, cell cycle, oocyte meiosis, and progesterone-mediated oocyte maturation, were analyzed. There were 149 nodes and 1246 edges in the PPI network, and 15 hub genes were identified according to the degree levels. The core gene (UBE2T) showed high expression in ES, validated by using GSE67886 and IHC. The ROC analysis revealed UBE2T had outstanding diagnostic value in ES (AUC = 0.75 in the training set, AUC = 0.90 in the validation set). Kaplan-Meier (analysis of survival rate) and Cox Regression analyses indicated that UBE2T was a sign of adverse results for sufferers with ES.
Conlusion:
UBE2T was a significant value biomarker for diagnosis and treatment of ES, thereby presenting a novel potential therapeutic target for ES as well as a new perspective for assessing the effect of treatment and prognostic prediction.
Insights
This study identified UBE2T as a key gene in Ewing sarcoma (ES) development. UBE2T shows high expression and serves as a valuable biomarker for ES diagnosis and prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Ewing sarcoma (ES) is a prevalent malignant bone tumor with incompletely understood molecular mechanisms.
- Identifying key genes and pathways is crucial for understanding ES development and progression.
Purpose of the Study:
- To identify candidate genes and biological pathways involved in Ewing sarcoma using bioinformatics.
- To evaluate the diagnostic and prognostic value of identified key genes in ES.
Main Methods:
- Downloaded and analyzed Gene Expression Omnibus (GEO) microarray datasets (GSE45544, GSE17618).
- Identified differentially expressed genes (DEGs) and performed functional enrichment analysis.
- Constructed a protein-protein interaction (PPI) network and identified hub genes.
- Validated the core gene UBE2T using a validation dataset (GSE67886) and immunohistochemistry (IHC).
- Assessed diagnostic value using ROC analysis and prognosis using Cox Regression.
Main Results:
- Identified 187 DEGs (56 downregulated, 131 upregulated) between ES tumor and normal samples.
- Enriched functions included cell division, cell proliferation, and cell cycle.
- Identified 15 hub genes in the PPI network; UBE2T was identified as the core gene.
- UBE2T demonstrated high expression in ES, validated by external data and IHC.
- UBE2T showed significant diagnostic value (AUC 0.75-0.90) and was associated with adverse prognosis in ES patients.
Conclusions:
- UBE2T is a significant biomarker for the diagnosis and treatment of Ewing sarcoma.
- UBE2T presents a novel potential therapeutic target for ES.
- UBE2T offers a new perspective for treatment effect assessment and prognostic prediction in ES.
