KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients

// Sarah Kammerer 1, 2 , Armin Sokolowski 1, 9 , Hubert Hackl 3 , Dieter Platzer 1 , Stephan Wenzel Jahn 4 , Amin El-Heliebi 5 , Daniela Schwarzenbacher 6 , Verena Stiegelbauer 6 , Martin Pichler 6, 7 , Simin Rezania 1, 2 , Heidelinde Fiegl 8 , Florentia Peintinger 4 , Peter Regitnig 4 , Gerald Hoefler 4 , Wolfgang Schreibmayer 1, 2 , Thomas Bauernhofer 2, 6 1 Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria 2 Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria 3 Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria 4 Institute of Pathology, Medical University of Graz, Austria 5 Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Austria 6 Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria 7 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 8 Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria 9 Present address: Division of Prosthodontics, Restorative Dentistry, Periodontology and Implantology, Medical University of Graz, Austria Correspondence to: Thomas Bauernhofer, email: thomas.bauernhofer@medunigraz.at Keywords: KCNJ3, GIRK1, biomarker, estrogen receptor positive breast cancer, RNA in situ hybridization Received: June 04, 2016      Accepted: October 26, 2016      Published: November 08, 2016 ABSTRACT 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 KCNJ3 using 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.