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

K T Shreya Parthasarathi,Susmita Mandal,Smrita Singh,Seetaramanjaneyulu Gundimeda,Akhilesh Pandey,Mohit Kumar Jolly,Jyoti Sharma

doi:10.3390/cancers14061444

Abstract

Simple SummaryBreast cancer involves changes in the healthy cells of the breast resulting in rapid and abnormal division of cells that later spread to other parts of the body through the process of metastasis, which involves epithelial mesenchymal transition (EMT). Ion channels play a significant role in the switch from epithelial to mesenchymal transition through their contributions to cellular motility, cell volume regulation and cell cycle progression. Comprehensive computational analyses were performed to understand the role of ion channels in tumor/metastatic samples of breast cancer and their correlation with EMT.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.

Highlights

Breast cancer is a life-threatening disease and is one of the most common types of cancer prevalent in individuals of all age groups, with the majority of cases in females
155 ion channels and 470 epithelialmesenchymal transition (EMT)-related genes were found in HM of microarray dataset (GSE52604) (Table 1)
Ten genes were identified as common DEGs in both ion channel and EMT lists (Supplementary Table S6)

Summary

Introduction

Breast cancer is a life-threatening disease and is one of the most common types of cancer prevalent in individuals of all age groups, with the majority of cases in females. It is one of the most aggressive tumors with multifaceted gene expression levels at different stages of tumor progression. Ion channels are multimeric proteins located in the plasma membrane of the cell They form a passageway extending from one side of the membrane to the other, thereby allowing the flow of ions into and out of the cell based on the electrochemical gradient. The activation of EMT programs is an expository mechanism for the gain of malignant phenotypes by epithelial cancer cells [9]. It was shown that ASIC1 and ASIC3 positively correlated with mesenchymal marker vimentin and inversely correlated with epithelial marker E-cadherin in those cells [14]

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