In Silico Analysis of Ion Channels and Their Correlation with Epithelial to Mesenchymal Transition in Breast Cancer

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.

Increased heterogeneity in expression of genes associated with cancer progression and drug resistance

“…Among the enriched biological processes, positive regulation of membrane potential is a key process in cancer progression with relevance for EMT. EMT has been reported to be dependent on modulation of ion channels of sodium, potassium, and calcium in different cancer types, and inhibiting the activity of these ion channels has been proposed as a potential therapy against cancer progression [ [144] , [145] , [146] , [147] ]. Similarly, G1/S transition is a major checkpoint in the regulation of the cell cycle.…”

TRPV3 regulates Breast Cancer Cell Proliferation and Apoptosis by EGFR/AKT pathway

“…TRPV4 may regulate breast cancer metastasis by regulating cell flexibility and extracellular protein expression through calcium dependent AKT-E-cadherin signal axis 22 . Although TRPV3 is a member of TRP superfamily, through network analysis, TRPV3 related to epithelial mesenchymal transformation of breast cancer 8 , but the role and mechanism of TRPV3 in breast cancer have not fully clarified. We observed that TRPV3 upregulated in human breast cancer samples and cell lines.…”

A bioinformatics analysis: ZFHX4 is associated with metastasis and poor survival in ovarian cancer

“…Ion channel disorder appeared to be responsible for the enhanced migration of cancer cells and ECM dysregulation [ 30 , 31 ]. Aberrant activation of Ca 2+ -permeable channels on the endoplasmic reticulum membrane and plasma membrane led to impulse Ca 2+ influx [ 32 ].…”