Comprehensive Bioinformatics Analysis and Machine Learning of TTK as a Transhepatic Arterial Chemoembolization
1Department of Gerontology, Jiangxi University of Traditional Chinese Medicine Affiliated Hospital, Nanchang, Jiangxi Province, China.
Abstract:
Transhepatic arterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, a significant proportion of patients are non-responders or poor responders to TACE. Therefore, our aim is to identify the targets of TACE responders or non-responders. GSE104580 was utilized to identify differentially expressed genes (DEGs) in TACE responders and non-responders. Following the protein-protein interaction (PPI) analysis, hub genes were identified using the MCC and MCODE plugins in Cytoscape software, as well as LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to investigate potential mechanisms. Subsequently, the hub genes were validated using data from The Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and The Human Protein Atlas (HPA) database. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival and Cox regression analysis were employed. A total of 375 DEGs were identified, with 126 remaining following PPI analysis, and TTK, a dual-specificity protein kinase associated with cell proliferation, was ultimately identified as the hub gene through multiple screening methods. Data analysis from TCGA, CCLE, and HPA databases revealed elevated TTK expression in HCC tissues. GSEA indicated that the cell cycle, farnesoid X receptor pathway, PPAR pathway, FOXM1 pathway, E2F pathway, and ferroptosis could be potential mechanisms for TACE non-responders. Analysis of immune cell infiltration showed a significant correlation between TTK and Th2 cells. KM and Cox analysis suggested that HCC patients with high TTK expression had a worse prognosis. TTK may play a pivotal role in HCC patients' response to TACE therapy and could be linked to the prognosis of these patients.
Insights
Identifying targets for transhepatic arterial chemoembolization (TACE) non-responders in hepatocellular carcinoma (HCC) revealed TTK as a key protein kinase. Elevated TTK expression correlates with poor prognosis and TACE resistance in HCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Transhepatic arterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC).
- A significant number of HCC patients do not respond or respond poorly to TACE.
- Identifying molecular targets is crucial for improving TACE efficacy.
Purpose of the Study:
- To identify differentially expressed genes (DEGs) and key molecular targets in TACE responders versus non-responders.
- To investigate the role of identified targets in HCC progression and TACE response.
- To evaluate the clinical significance and prognostic value of potential therapeutic targets.
Main Methods:
- Utilized gene expression data (GSE104580) to identify DEGs between TACE responders and non-responders.
- Performed protein-protein interaction (PPI) analysis and utilized LASSO regression to identify hub genes.
- Validated hub gene expression and clinical significance using The Cancer Genome Atlas (TCGA), CCLE, and HPA databases.
- Conducted Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis.
Main Results:
- Identified 375 DEGs, with TTK (a dual-specificity protein kinase) identified as a key hub gene through multiple screening methods.
- Confirmed elevated TTK expression in HCC tissues across TCGA, CCLE, and HPA datasets.
- GSEA suggested involvement of cell cycle, nuclear receptor pathways (FXR, PPAR), FOXM1, E2F, and ferroptosis in TACE non-response.
- Found a significant correlation between TTK expression and Th2 cell infiltration.
- Kaplan-Meier and Cox regression analyses indicated that high TTK expression is associated with a worse prognosis in HCC patients.
Conclusions:
- TTK is a potential biomarker for predicting TACE response and prognosis in HCC.
- Targeting TTK may offer a novel therapeutic strategy for improving TACE efficacy in non-responsive HCC patients.
- Further research into TTK's role in the tumor microenvironment and cell proliferation pathways is warranted.
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