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Identification of hub genes to determine drug-disease correlation in breast carcinomas
Chiranjib Bhowmick1, Motiur Rahaman1, Shatarupa Bhattacharya1
1School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Medinipur, Kharagpur, West Bengal, 721302, India.
Abstract:
The exact molecular mechanism underlying the heterogeneous drug response against breast carcinoma remains to be fully understood. It is urgently required to identify key genes that are intricately associated with varied clinical response of standard anti-cancer drugs, clinically used to treat breast cancer patients. In the present study, the utility of transcriptomic data of breast cancer patients in discerning the clinical drug response using machine learning-based approaches were evaluated. Here, a computational framework has been developed which can be used to identify key genes that can be linked with clinical drug response and progression of cancer, offering an immense opportunity to predict potential prognostic biomarkers and therapeutic targets. The framework concerned utilizes DeSeq2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Cytoscape, and machine learning techniques to find these crucial genes. Total RNA extraction and qRT-PCR were performed to quantify relative expression of few hub genes selected from the networks. In our study, we have experimentally checked the expression of few key hub genes like APOA2, DLX5, APOC3, CAMK2B, and PAK6 that were predicted to play an immense role in breast cancer tumorigenesis and progression in response to anti-cancer drug Paclitaxel. However, further experimental validations will be required to get mechanistic insights of these genes in regulating the drug response and cancer progression which will likely to play pivotal role in cancer treatment and precision oncology.
Insights
Researchers developed a computational framework to identify key genes linked to breast cancer drug response. This approach aids in predicting prognostic biomarkers and therapeutic targets for personalized cancer treatment.
Area of Science:
- Genomics and Computational Biology
- Cancer Research
- Pharmacogenomics
Background:
- Understanding heterogeneous drug response in breast carcinoma is crucial.
- Identifying key genes associated with varied clinical responses to standard anti-cancer drugs is needed.
Purpose of the Study:
- To evaluate the utility of transcriptomic data for discerning clinical drug response using machine learning.
- To develop a computational framework for identifying genes linked to drug response and cancer progression.
Main Methods:
- Utilized DeSeq2, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Cytoscape.
- Applied machine learning techniques to identify crucial genes.
- Performed qRT-PCR to quantify the expression of selected hub genes (APOA2, DLX5, APOC3, CAMK2B, PAK6).
Main Results:
- Developed a computational framework to identify key genes associated with clinical drug response.
- Experimentally validated the expression of predicted hub genes (APOA2, DLX5, APOC3, CAMK2B, PAK6) in response to Paclitaxel.
- Identified potential prognostic biomarkers and therapeutic targets for breast cancer.
Conclusions:
- The developed framework offers an opportunity to predict prognostic biomarkers and therapeutic targets.
- Experimental validation of key hub genes provides insights into their role in breast cancer progression and drug response.
- Further research is needed for mechanistic insights to advance cancer treatment and precision oncology.
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