KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients
(2016)
Numerous studies showed abnormal expression of ion channels in different cancer types. Amongst these, the potassium channel gene KCNJ3 (encoding for GIRK1 proteins) has been reported to be upregulated in tumors of patients with breast cancer and to correlate with positive lymph node status. We aimed to study KCNJ3 levels in different breast cancer subtypes using gene expression data from the TCGA, to validate our findings using RNA in situ hybridization in a validation cohort (GEO ID GSE17705), and to study the prognostic value of KCNJ3using survival analysis. In a total of > 1000 breast cancer patients of two independent data sets we showed a) that KCNJ3 expression is upregulated in tumor tissue compared to corresponding normal tissue (p < 0.001), b) that KCNJ3 expression is associated with estrogen receptor (ER) positive tumors (p < 0.001), but that KCNJ3 expression is variable within this group, and c) that ER positive patients with high KCNJ3 levels have worse overall (p < 0.05) and disease free survival probabilities (p < 0.01), whereby KCNJ3 is an independent prognostic factor (p <0.05). In conclusion, our data suggest that patients with ER positive breast cancer might be stratified into high risk and low risk groups based on the KCNJ3 levels in the tumor.
Mechanical interaction between cells - specifically distortion of tensional homeostasis-emerged as an important aspect of breast cancer genesis and progression. We investigated the biophysical characteristics of mechanosensitive ion channels (MSCs) in the malignant MCF-7 breast cancer cell line. MSCs turned out to be the most abundant ion channel species and could be activated by negative pressure at the outer side of the cell membrane in a saturable manner. Assessing single channel conductance (GΛ) for different monovalent cations revealed an increase in the succession: Li⁺ < Na⁺ < K⁺ ≈Rb⁺ ≈ Cs⁺. Divalent cations permeated also with the order: Ca²⁺ < Ba²⁺. Comparison of biophysical properties enabled us to identify MSCs in MCF-7 as ion channels formed by the Piezo1 protein. Using patch clamp technique no functional MSCs were observed in the benign MCF-10A mammary epithelial cell line. Blocking of MSCs by GsMTx-4 resulted in decreased motility of MCF-7, but not of MCF-10A cells, underscoring a possible role of Piezo1 in invasion and metastatic propagation. The role of Piezo1 in biology and progression of breast cancer is further substantiated by markedly reduced overall survival in patients with increased Piezo1 mRNA levels in the primary tumor.
Pinpoint the Joules: Unifying Runtime-Support for Energy Measurements on Heterogeneous Systems
(2020)
For the design and operation of today's computer systems, power and energy requirements are highest priorities. Unlike performance analyses, however, power and energy measurements of heterogeneous systems are difficult to conduct. Especially at the system-software level, performing power and energy measurements remains challenging. Yet, such measurements are essential to improve software components for low power and high energy-efficiency.In this paper, we analyze and discuss the power and energy characteristics of several heterogeneous systems with up to 20 cores (160 hardware threads) and 1 TB of main memory. For the analyzed systems, we outline challenges regarding power and energy measurements and show ways to overcome limitations (i.e., sampling constraints). To improve the current state of the art in power and energy measurements at the system-software level, we present the design and implementation of PINPOINT, an energy-profiling tool which unifies different power and energy measurement interfaces.