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KLF7: a new candidate biomarker and therapeutic target for high-grade serous ovarian cancer
Marta De Donato1,2, Gabriele Babini3, Simona Mozzetti2
1Unità di Medicina Traslazionale per la Salute della Donna e del Bambino, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Roma, Italy.
Background:
In spite of great progress in the surgical and clinical management, until now no significant improvement in overall survival of High-Grade Serous Ovarian Cancer (HGSOC) patients has been achieved. Important aspects for disease control remain unresolved, including unclear pathogenesis, high heterogeneity and relapse resistance after chemotherapy. Therefore, further research on molecular mechanisms involved in cancer progression are needed to find new targets for disease management. The Krüppel-like factors (KLFs) are a family of transcriptional regulators controlling several basic cellular processes, including proliferation, differentiation and migration. They have been shown to play a role in various cancer-relevant processes, in a context-dependent way.
Methods:
To investigate a possible role of KLF family members as prognostic biomarkers, we carried out a bioinformatic meta-analysis of ovarian transcriptome datasets in different cohorts of late-stage HGSOC patients. In vitro cellular models of HGSOC were used for functional studies exploring the role of KLF7 in disease development and progression. Finally, molecular modelling and virtual screening were performed to identify putative KLF7 inhibitors.
Results:
Bioinformatic analysis highlighted KLF7 as the most significant prognostic gene, among the 17 family members. Univariate and multivariate analyses identified KLF7 as an unfavourable prognostic marker for overall survival in late-stage TCGA-OV and GSE26712 HGSOC cohorts. Functional in vitro studies demonstrated that KLF7 can play a role as oncogene, driving tumour growth and dissemination. Mechanistic targets of KLF7 included genes involved in epithelial to mesenchymal transition, and in maintaining pluripotency and self-renewal characteristics of cancer stem cells. Finally, in silico analysis provided reliable information for drug-target interaction prediction.
Conclusions:
Results from the present study provide the first evidence for an oncogenic role of KLF7 in HGSOC, suggesting it as a promising prognostic marker and therapeutic target.
Insights
Krüppel-like factor 7 (KLF7) acts as an oncogene in High-Grade Serous Ovarian Cancer (HGSOC), driving tumor progression and offering a new target for therapy.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- High-Grade Serous Ovarian Cancer (HGSOC) lacks significant survival improvements despite advances.
- Unclear pathogenesis, heterogeneity, and chemoresistance hinder HGSOC disease control.
- Novel molecular targets are crucial for effective HGSOC management.
Purpose of the Study:
- To investigate Krüppel-like factor (KLF) family members as prognostic biomarkers in HGSOC.
- To explore the functional role of KLF7 in HGSOC development and progression.
- To identify potential KLF7 inhibitors for therapeutic development.
Main Methods:
- Bioinformatic meta-analysis of HGSOC transcriptome datasets.
- In vitro functional studies using HGSOC cellular models.
- Molecular modeling and virtual screening for drug-target identification.
Main Results:
- KLF7 identified as the most significant prognostic gene among 17 KLF family members.
- KLF7 is an unfavorable prognostic marker for overall survival in late-stage HGSOC.
- KLF7 promotes tumor growth and dissemination by regulating epithelial-mesenchymal transition and cancer stem cell properties.
Conclusions:
- KLF7 demonstrates an oncogenic role in HGSOC.
- KLF7 shows promise as a prognostic biomarker for HGSOC.
- KLF7 represents a potential therapeutic target for HGSOC treatment.
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