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Integrative single-cell and bulk RNA-seq analysis identifies glycosyltransferases-related signature in triple
Junyi Hu1, Ningning Yuan2, Zhenglan Huang2
1Department of Clinical Medicine, International Medical College, Chongqing Medical University, Chongqing, 400016, China.
Abstract:
Triple-negative breast cancer (TNBC) represents a formidable subtype with a grim prognosis. This study aims to pinpoint the molecular targets of Glycosyltransferases (GTs) in TNBC, with the goal of improving prognostic accuracy and boosting the effectiveness of immune therapies. Using publicly available datasets, we combined differentially expressed and correlated genes based on AUCell scores from single-cell sequencing. These were then subjected to enrichment analysis and utilized for constructing a risk model. A total of 780 genes were identified as being closely associated with GTs. Using 101 algorithm combinations, a 17-gene signature emerged with predictive capabilities for TNBC patient prognosis. At the same time, we examined the role of these model genes in the tumor microenvironment(TME). We identified key transcription factors correlating with GTs, including CREB3L1, which showed significant association with the CERCAM gene. Subsequently, the pro-cancerous effects of GTs were validated through a series of experiments, including CCK-8 cell viability assays, scratch wound healing assays, and Transwell migration and invasion assays. This research lays the foundation for targeted drug therapies, offering new opportunities to enhance clinical outcomes in TNBC.
Insights
This study identifies a 17-gene signature linked to Glycosyltransferases (GTs) for predicting triple-negative breast cancer (TNBC) prognosis. These findings offer new avenues for targeted therapies to improve patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its aggressive nature and limited targeted treatment options.
- Glycosyltransferases (GTs) play crucial roles in cellular processes, and their involvement in TNBC pathogenesis warrants further investigation.
- Improving prognostic accuracy and enhancing immunotherapy efficacy are critical unmet needs in TNBC management.
Purpose of the Study:
- To identify molecular targets of Glycosyltransferases (GTs) in triple-negative breast cancer (TNBC).
- To develop a gene signature for predicting TNBC patient prognosis and response to therapy.
- To explore the role of GT-associated genes in the tumor microenvironment (TME) and their functional impact.
Main Methods:
- Analysis of publicly available single-cell sequencing datasets to identify differentially expressed and correlated genes associated with GTs.
- Application of AUCell scores for gene expression analysis and enrichment analysis.
- Construction of a predictive risk model using multiple algorithm combinations to identify a novel 17-gene signature.
- Validation of GTs' pro-cancerous effects through in vitro assays (CCK-8, scratch wound healing, Transwell migration/invasion).
Main Results:
- A total of 780 genes were found to be closely associated with GTs in TNBC.
- A robust 17-gene signature was identified with significant predictive capability for TNBC patient prognosis.
- Key transcription factors, including CREB3L1, were identified, showing correlation with GTs and the CERCAM gene within the TME.
- Experimental validation confirmed the pro-cancerous roles of GTs in TNBC cell viability, migration, and invasion.
Conclusions:
- The identified 17-gene signature provides a novel tool for prognostic assessment in TNBC.
- Understanding the role of GTs and their associated genes in the TME can inform the development of targeted therapeutic strategies.
- This research lays the groundwork for novel targeted drug therapies to improve clinical outcomes for TNBC patients.
