KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients.
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.
Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria.
Sarah
S
Kammerer
Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria.|Present address: Division of Prosthodontics, Restorative Dentistry, Periodontology and Implantology, Medical University of Graz, Austria.
Armin
A
Sokolowski
Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Austria.
Hubert
H
Hackl
Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria.
Dieter
D
Platzer
Institute of Pathology, Medical University of Graz, Austria.
Stephan Wenzel
SW
Jahn
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Austria.
Amin
A
El-Heliebi
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
Daniela
D
Schwarzenbacher
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
Verena
V
Stiegelbauer
Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.|Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Martin
M
Pichler
Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria.
Simin
S
Rezania
Department of Gynecology and Obstetrics, Medical University of Innsbruck, Austria.
Heidelinde
H
Fiegl
Institute of Pathology, Medical University of Graz, Austria.
Florentia
F
Peintinger
Institute of Pathology, Medical University of Graz, Austria.
Peter
P
Regitnig
Institute of Pathology, Medical University of Graz, Austria.
Gerald
G
Hoefler
Molecular Physiology Group, Institute of Biophysics, Medical University of Graz, Austria.|Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria.
Wolfgang
W
Schreibmayer
Research Unit on Ion Channels and Cancer Biology, Medical University of Graz, Austria.|Division of Oncology, Department of Internal Medicine, Medical University of Graz, Austria.
Thomas
T
Bauernhofer
D000367:Age Factors; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality; D015331:Cohort Studies; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016019:Survival Analysis; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018719:Erb-b2 Receptor Tyrosine Kinases; C497066:KCNJ3 protein, human
GIRK1; KCNJ3; RNA in situ hybridization; biomarker; estrogen receptor positive breast cancer