A multiOmics approach to identify altered ion channels across breast cancer subtypes

Abstract A multiOmics approach unifies patient-specific datasets to deepen insights into molecular aspects of cancer. Breast cancer cells often exhibit membrane potential deregulation driven by alterations in ion channel activity and distribution. Deregulation of ion channels could result in chemo-resistance, proliferation stimulation and tumor growth maintenance. Here, differentially expressed ion channels (DEICs), differentially methylated regions (DMRs) associated with those ion channels and, copy number alterations in the DEICs and their associated DMRs were identified using publicly available transcriptomic, methylomic and genomic datasets of patients with breast cancer subtypes. The expression of DEICs was further compared using cell line expression profiles available from the DepMap project. Additionally, prognostically significant ion channels were identified using Kaplan-Meier survival plots. 79 ion channels including 22, 9, 9, 20 and 19 were differentially expressed in luminalA, luminalB, HER2, basal and normal-like subtypes, respectively. Of those, 27 ion channels including 10, 6, 4, 5 and 2 were associated with 161 differentially methylated enhancers and promoters in luminalA, luminalB, HER2, basal and normal-like subtypes, respectively. Several patients exhibited amplifications and deletions affecting the 27 ion channels and their associated DMRs. 9 ion channels indicated a positive correlation of expression alterations in cell lines expression profiles. ANO6, SLC10A5, and SLC31A1 in luminalA, KCNH4 in HER2-enriched and GRINA in basal-like were associated with survival in patients with subtypes of breast cancer. Most likely, the study marks the first step towards establishing oncochannels across breast cancer subtypes and encourages future research to investigate potential ion channels through experimental validation.