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Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Variant Analysis of miRNA Regulatory Genes in 35 Sporadic Lung Carcinoma Tumors
Özkan Bağcı1, Ebru Marzioğlu Özdemir2, Batuhan Şanlıtürk2
1Department of Medical Genetics, Selcuk University, School of Medicine, Konya, Turkey. ozkan.bagci@selcuk.edu.tr.
Abstract:
Lung cancer is one of the cancer types with the highest mortality worldwide. The most frequently mutated genes known to be clinically important in lung cancers are EGFR, BRAF, and KRAS genes. Therefore, the therapeutic agents developed are directed against variants that cause over-activation of the EGFR-KRAS-BRAF-BRAF-MEK/ERK signalling pathway. However, different responses of patients to Tyrosine Kinase Inhibitors (TKIs) suggest that new prognostic biomarkers should be defined and epigenetic mechanisms may be related to this situation.
Methods:
In this study, sequence analyses of AGO2, DICER, and DROSHA genes involved in miRNA biogenesis and EGFR, KRAS, and BRAF genes were performed in 35 patients with sporadic lung cancer.
Results:
We found variations in genes involved in miRNA biogenesis that have not been previously reported in the literature. In addition, we found 4 different variants in the EGFR gene that have been described in the literature. In addition, a statistically significant association was found between the presence of mutations in at least one of the genes involved in miRNA biogenesis and metastasis (p:0.02).
Conclusions:
In conclusion, genomic dysregulation of key miRNA biogenesis genes may be one of the possible reasons for the differential response of patients to therapeutic agents and the development of metastasis in EGFR wild type tumours.
Insights
Genomic changes in miRNA biogenesis genes may explain varied responses to lung cancer therapies and metastasis. These findings highlight potential new biomarkers for predicting patient outcomes and guiding treatment strategies.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer has high global mortality.
- EGFR, BRAF, and KRAS genes are key in lung cancer, targeted by therapies.
- Patient responses to Tyrosine Kinase Inhibitors (TKIs) vary, suggesting a need for new biomarkers and investigation into epigenetic factors.
Purpose of the Study:
- To investigate genetic variations in miRNA biogenesis genes (AGO2, DICER, DROSHA) and key cancer genes (EGFR, KRAS, BRAF) in sporadic lung cancer.
- To identify potential novel biomarkers for predicting patient response to therapy and metastasis.
Main Methods:
- Sequence analysis of AGO2, DICER, DROSHA, EGFR, KRAS, and BRAF genes.
- Study included 35 patients with sporadic lung cancer.
Main Results:
- Novel variations in miRNA biogenesis genes were identified.
- Four known EGFR variants were found.
- A significant association (p:0.02) was observed between mutations in miRNA biogenesis genes and metastasis.
Conclusions:
- Genomic alterations in miRNA biogenesis genes could contribute to differential patient responses to therapies.
- These dysregulations may play a role in metastasis, particularly in EGFR wild-type tumors.
- MiRNA biogenesis gene variations represent potential prognostic biomarkers in lung cancer.
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