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Discovering biomarkers for hormone-dependent tumors: in silico study on signaling pathways implicated in cell cycle
Klaudia Waszczykowska1, Karolina Prażanowska1, Żaneta Kałuzińska2
1Faculty of Biomedical Sciences, Medical University of Lodz, 90-752, Lodz, Poland.
Abstract:
Malignancies dependent on hormone homeostasis include breast, ovary, cervical, prostate, testis and uterine tumors. Hormones are involved in signal transduction which orchestrate processes, such as apoptosis, proliferation, cell cycle or cytoskeleton organization. Currently, there is a need for novel biomarkers which would help to diagnose cancers efficiently. In this study, the genes implicated in signaling that is important in hormone-sensitive carcinogenesis were investigated regarding their prognostic significance. Data of seven cancer cohorts were collected from FireBrowse. 54 gene sets implicated in specific pathways were browsed through MSig database. Profiling was assessed via Monocle3, while gene ontology through PANTHER. For confirmation, correlation analysis was performed using WGCNA. Protein-protein networks were visualized via Cytoscape and impact of genes on survival, as well as cell cycle or cytoskeleton-related prognostic signatures, was tested. Several differences in expression profile were identified, some of them allowed to distinguish histology. Functional annotation revealed that various regulation of cell cycle, adhesion, migration, apoptosis and angiogenesis underlie these differences. Clinical traits, such as histological type or cancer staging, were found during evaluation of module-trait relationships. Of modules, the TopHubs (COL6A3, TNR, GTF2A1, NKX3-1) interacted directly with, e.g., PDGFB, ITGA10, SP1 or AKT3. Among TopHubs and interacting proteins, many showed an impact on hazard ratio and affected the cell cycle or cytoskeleton-related prognostic signatures, e.g., COL1A1 or PDGFB. In conclusion, this study laid the foundation for further hormone-sensitive carcinogenesis research through identification of genes which prove that crosstalk between cell cycle and cytoskeleton exists, opening avenues for future therapeutic strategies.
Insights
This study identifies key genes involved in hormone-sensitive cancers, revealing a link between cell cycle and cytoskeleton signaling. These findings pave the way for new diagnostic biomarkers and therapeutic strategies in carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Hormone homeostasis is crucial for malignancies like breast, ovarian, cervical, prostate, testicular, and uterine cancers.
- Hormones regulate critical cellular processes including apoptosis, proliferation, cell cycle, and cytoskeleton organization.
- Novel biomarkers are needed for efficient diagnosis of hormone-sensitive cancers.
Purpose of the Study:
- To investigate the prognostic significance of genes involved in hormone-sensitive carcinogenesis signaling pathways.
- To identify potential novel biomarkers for early cancer detection and patient stratification.
- To explore the interplay between cell cycle and cytoskeleton in cancer development.
Main Methods:
- Utilized gene expression data from seven cancer cohorts (FireBrowse).
- Analyzed 54 gene sets from the MSig database, employing Monocle3 for profiling and PANTHER for gene ontology.
- Performed correlation analysis (WGCNA), visualized protein-protein networks (Cytoscape), and assessed gene impact on survival and prognostic signatures.
Main Results:
- Identified distinct gene expression profiles, some differentiating cancer histology.
- Functional annotation revealed links between cell cycle regulation, adhesion, migration, apoptosis, angiogenesis, and observed expression differences.
- TopHub genes (e.g., COL6A3, TNR) interacted with proteins (e.g., PDGFB, AKT3) impacting survival and prognostic signatures.
Conclusions:
- The study identified genes demonstrating a crosstalk between cell cycle and cytoskeleton in hormone-sensitive carcinogenesis.
- These findings provide a foundation for further research into hormone-dependent cancers.
- The identified genes and pathways offer potential avenues for future therapeutic strategies.
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