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Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
Unravelling driver genes as potential therapeutic targets in ovarian cancer via integrated bioinformatics approach
Anam Beg1, Rafat Parveen2, Hassan Fouad3
1Department of Computer Science, Jamia Millia Islamia, New Delhi, 110025, India.
Abstract:
Target-driven cancer therapy is a notable advancement in precision oncology that has been accompanied by substantial medical accomplishments. Ovarian cancer is a highly frequent neoplasm in women and exhibits significant genomic and clinical heterogeneity. In a previous publication, we presented an extensive bioinformatics study aimed at identifying specific biomarkers associated with ovarian cancer. The findings of the network analysis indicate the presence of a cluster of nine dysregulated hub genes that exhibited significance in the underlying biological processes and contributed to the initiation of ovarian cancer. Here in this research article, we are proceeding our previous research by taking all hub genes into consideration for further analysis. GEPIA2 was used to identify patterns in the expression of critical genes. The KM plotter analysis indicated that the out of all genes 5 genes are statistically significant. The cBioPortal platform was further used to investigate the frequency of genetic mutations across the board and how they affected the survival of the patients. Maximum mutation was reported by ELAVL2. In order to discover viable therapeutic candidates after competitive inhibition of ELAVL2 with small molecular drug complex, high throughput screening and docking studies were used. Five compounds were identified. Overall, our results suggest that the ELAV-like protein 2-ZINC03830554 complex was relatively stable during the molecular dynamic simulation. The five compounds that have been found can also be further examined as potential therapeutic possibilities. The combined findings suggest that ELAVL2, together with their genetic changes, can be investigated in therapeutic interventions for precision oncology, leveraging early diagnostics and target-driven therapy.
Insights
Researchers identified ELAVL2 as a key gene in ovarian cancer, finding specific compounds that may inhibit its function. This discovery offers potential for new precision oncology treatments targeting ovarian cancer.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Ovarian cancer presents significant genomic and clinical heterogeneity.
- Previous bioinformatics analysis identified nine dysregulated hub genes in ovarian cancer initiation.
- This study further investigates these hub genes for therapeutic targets.
Purpose of the Study:
- To identify significant genes and mutations in ovarian cancer.
- To discover potential therapeutic candidates for ovarian cancer treatment.
- To explore ELAVL2 as a target for precision oncology.
Main Methods:
- Gene expression analysis using GEPIA2.
- Survival analysis using KM plotter.
- Mutation frequency and impact analysis using cBioPortal.
- High-throughput screening and molecular docking for drug discovery.
Main Results:
- Five statistically significant genes were identified, with ELAVL2 showing maximum mutation frequency.
- ELAVL2 mutations were linked to patient survival outcomes.
- Five potential therapeutic compounds were identified, with the ELAVL2-ZINC03830554 complex showing stability.
Conclusions:
- ELAVL2 is a promising target for precision oncology in ovarian cancer.
- Genetic alterations in ELAVL2 warrant further investigation for therapeutic interventions.
- Identified compounds offer potential as novel therapeutic strategies for ovarian cancer.
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