40P - Overexpression of G protein-activated inward rectifier potassium channel 1 (GIRK1) is associated with lymph node metastasis and poor prognosis in br...

Date 08 May 2014
Event IMPAKT 2014
Session Welcome reception and Poster Walk
Topics Breast Cancer
Translational Research
Presenter Sarah Kammerer
Citation Annals of Oncology (2014) 25 (suppl_1): i8-i16. 10.1093/annonc/mdu066
Authors S. Kammerer1, A. Sokolowski1, H. Hackl2, S. Jahn3, M. Asslaber3, F. Symmans4, F. Peintinger3, P. Regitnig3, W. Schreibmayer1, T. Bauernhofer5
  • 1Institute Of Biophysics, Medical University of Graz, 8010 - Graz/AT
  • 2Division Of Bioinformatics, Innsbruck Medical University, 6020 - Innsbruck/AT
  • 3Institute Of Pathology, Medical University of Graz, 8036 - Graz/AT
  • 4Cancer Center, University of Texas MD Anderson, TX 77030 - Houston/US
  • 5Department Of Medicine, Division Of Oncology, Medical University of Graz, 8036 - Graz/AT

Abstract

Background/aim:

Effective curative treatments are still lacking for metastasised breast cancer. Hence, new early biomarkers are required to treat patients at a curable state. Several potassium channels are known to be deregulated in breast cancer. Amongst them, overexpression of GIRK1 mRNA and protein has been shown to correlate with lymph node metastasis and poor prognosis in studies with small patient numbers. In this study, we aim to validate the use of GIRK1 as prognostic and/or predictive breast cancer biomarker. GIRK1 mRNA expression was analysed using microarray data and GIRK1 protein expression is studied by immunohistochemistry (IHC) in large breast cancer patient sets.

Methods:

Microarray data of breast carcinoma available from the cancer genome atlas (TCGA) and of a data set available from the gene expression omnibus (GEO; GSE10510) were analysed in SPSS 20.0. Analysis of a second GEO data set (GSE17705) and IHC analysis of formalin-fixed, paraffin-embedded primary tumour samples corresponding to the two GEO data sets (n = 450) are in progress.

Results:

Analysis of the TCGA microarray data showed that GIRK1 is significantly overexpressed in breast tumours compared to normal tissue (n = 105, p < 0.001). Furthermore, GIRK1 expression is significantly higher in estrogen receptor positive [ER(+)] patients (n = 841, p < 0.001) and in lymph node positive [LN(+)] patients (n = 766, p < 0.001) when compared to ER(−) and LN(−) patients, respectively. Survival analysis of the TCGA data set showed that patients with high GIRK1 expression have a worse prognosis than patients with low GIRK1 expression (n = 735, p = 0.034). Analysis of the GEO set GSE10510 confirmed the finding that GIRK1 expression is higher in LN(+) patients (n = 114, p = 0.002), but no significant difference in GIRK1 expression was found between ER(+) and ER(−) patients (n = 148, p = 0.861).

Conclusion:

Our analysis of microarray data of two large patient sets confirms previous findings and indicates that GIRK1 overexpression is correlated to lymph node metastasis and poor prognosis of breast cancer patients. In addition, we found an elevated GIRK1 expression in ER(+) breast cancer patients in the larger of our data sets. IHC analyses on 450 breast cancer patient samples may provide further information to support the clinical significance of GIRK1 mRNA expression.

Disclosure:

All authors have declared no conflicts of interest.