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Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
In Silico Analysis of Ion Channels and Their Correlation with Epithelial to Mesenchymal Transition in Breast Cancer
K T Shreya Parthasarathi1, Susmita Mandal2, Smrita Singh1,3,4,5
1Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
Abstract:
Uncontrolled growth of breast cells due to altered gene expression is a key feature of breast cancer. Alterations in the expression of ion channels lead to variations in cellular activities, thus contributing to attributes of cancer hallmarks. Changes in the expression levels of ion channels were observed as a consequence of EMT. Additionally, ion channels were reported in the activation of EMT and maintenance of a mesenchymal phenotype. Here, to identify altered ion channels in breast cancer patients, differential gene expression and weighted gene co-expression network analyses were performed using transcriptomic data. Protein-protein interactions network analysis was carried out to determine the ion channels interacting with hub EMT-related genes in breast cancer. Thirty-two ion channels were found interacting with twenty-six hub EMT-related genes. The identified ion channels were further correlated with EMT scores, indicating mesenchymal phenotype. Further, the pathway map was generated to represent a snapshot of deregulated cellular processes by altered ion channels and EMT-related genes. Kaplan-Meier five-year survival analysis and Cox regressions indicated the expression of CACNA1B, ANO6, TRPV3, VDAC1 and VDAC2 to be potentially associated with poor survival. Deregulated ion channels correlate with EMT-related genes and have a crucial role in breast cancer-associated tumorigenesis. Most likely, they are potential candidates for the determination of prognosis in patients with breast cancer.
Insights
Altered ion channels are linked to breast cancer progression and poor survival. These findings suggest ion channels could help predict patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Uncontrolled breast cell growth defines breast cancer, driven by altered gene expression.
- Ion channel expression changes are linked to epithelial-mesenchymal transition (EMT), a key process in cancer metastasis.
Purpose of the Study:
- To identify ion channels dysregulated in breast cancer.
- To investigate the relationship between ion channels, EMT, and patient survival.
Main Methods:
- Differential gene expression and weighted gene co-expression network analyses on transcriptomic data.
- Protein-protein interaction network analysis to identify ion channels interacting with EMT genes.
- Correlation with EMT scores and survival analysis (Kaplan-Meier, Cox regression).
Main Results:
- Thirty-two ion channels were found to interact with twenty-six hub EMT-related genes.
- Specific ion channels (CACNA1B, ANO6, TRPV3, VDAC1, VDAC2) were associated with poor five-year survival.
- Deregulated ion channels correlate with EMT markers and patient prognosis.
Conclusions:
- Ion channels play a critical role in breast cancer development and progression.
- Dysregulated ion channels are potential biomarkers for predicting breast cancer patient prognosis.
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