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pmid:27835900

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

Sarah Kammerer · Armin Sokolowski · Hubert Hackl · Dieter Platzer · Stephan Wenzel Jahn · Amin El-Heliebi · Daniela Schwarzenbacher · Verena Stiegelbauer · Martin Pichler · Simin Rezania · Heidelinde Fiegl · Florentia Peintinger · Peter Regitnig · Gerald Hoefler · Wolfgang Schreibmayer · Thomas Bauernhofer

Oncotarget · 2016 doi:10.18632/oncotarget.13224

Paper

complete

Experiment

partial

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:27835900
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science-record
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2026-11-01T15:40:21Z
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2026-11-01T21:59:12Z
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paper object · 10 fields
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title
KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients.
doi
10.18632/oncotarget.13224
pmid
27835900
authors array · 16 items
[0]
Sarah Kammerer
[1]
Armin Sokolowski
[2]
Hubert Hackl
[3]
Dieter Platzer
[4]
Stephan Wenzel Jahn
[5]
Amin El-Heliebi
[6]
Daniela Schwarzenbacher
[7]
Verena Stiegelbauer
[8]
Martin Pichler
[9]
Simin Rezania
[10]
Heidelinde Fiegl
[11]
Florentia Peintinger
[12]
Peter Regitnig
[13]
Gerald Hoefler
[14]
Wolfgang Schreibmayer
[15]
Thomas Bauernhofer
journal
Oncotarget
year
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 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.
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A time-independent Cox-proportional hazard approach was applied for univariate and multivariate survival analysis.
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sections[16] "Statistical analysis" paragraph 2
quote
A time-independent Cox-proportional hazard approach was applied for univariate and multivariate survival analysis.
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complete
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The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.
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sections[9] "Gene expression data from the cancer genome atlas" paragraph 2
quote
The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.
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In ER-positive breast cancer patients, high KCNJ3 expression is associated with worse overall and disease-free survival, with KCNJ3 serving as an independent prognostic factor.
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qualitative
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sections[0] "Abstract" paragraph 1
quote
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.
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sections[0] "Abstract" paragraph 1
quote
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).
[2] object · 3 fields
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sections[0] "Abstract" paragraph 1
quote
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.
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complete
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In ER-positive breast cancer patients, high KCNJ3 expression is associated with worse overall and disease-free survival, with KCNJ3 serving as an independent prognostic factor.
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The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.
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The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.
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Cox-proportional hazard models for estrogen receptor positive breast cancer patients
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KCNJ3 is an independent prognostic factor in ER positive patients
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Table 1
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Cox-proportional hazard models for estrogen receptor positive breast cancer patients
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[7]
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KCNJ3 expression
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low(≤ 72th %ile) vs. high (> 72th %ile)
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1.8(1.0–3.0)
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0.036
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5.2(1.3–21.8)
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Patient characteristics of the two data sets studied
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Gene expression data from the cancer genome atlas
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Patient characteristics of the two data sets studied
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[0]
[1]
TCGA data set (%)(n = 905)
[2]
Validation set (%)(n = 66)
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[0]
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[2]
[3]
<0.001
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[1]
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89.4
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[0]
n.a.
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12.4
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0
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[5] array · 4 items
[0]
mean ± SD
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58 ± 13
[2]
63.7 ± 9.8
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[0]
Status
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[2]
[3]
< 0.001
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42.4
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57.6
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9.0
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0
[3]
[10] array · 4 items
[0]
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[2]
[3]
< 0.001
[11] array · 4 items
[0]
mean ± SD
[1]
32 ± 35
[2]
157 ± 76
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[0]
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[2]
[3]
n.s.
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[0]
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46.1
[2]
51.5
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49.7
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45.5
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n.a.
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4.2
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3.0
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[2]
[3]
n.s.
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[0]
negative
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86.4
[2]
100
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1.7
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0
[3]
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[0]
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11.9
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0
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n.s.
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26.0
[2]
40.9
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56.2
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48.5
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11.3
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6.1
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3.6
[2]
4.5
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n.a.
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2.9
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Grade
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[2]
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n.s.
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1
[1]
16.6
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18.2
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2
[1]
55.8
[2]
54.6
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3
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21.4
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24.2
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[0]
4
[1]
1.7
[2]
0
[3]
[31] array · 4 items
[0]
n.a.
[1]
4.5
[2]
3.0
[3]
[32] array · 4 items
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ER status
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[2]
[3]
< 0.001
[33] array · 4 items
[0]
negative
[1]
21.4
[2]
0
[3]
[34] array · 4 items
[0]
positive
[1]
71.5
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100
[3]
[35] array · 4 items
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n.a.
[1]
7.1
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0
[3]
[36] array · 4 items
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PR status
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[2]
[3]
n.s.
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[0]
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30.6
[2]
24.2
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62.0
[2]
75.8
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[39] array · 4 items
[0]
n.a.
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7.4
[2]
0
[3]
[40] array · 4 items
[0]
Her2 status
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[2]
[3]
n.a.
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70.2
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11.8
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n.a.
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18.0
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100
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PAM50 classification
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[2]
[3]
n.a.
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[0]
luminal A
[1]
25.2
[2]
[3]
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[0]
luminal B
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13.4
[2]
[3]
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Her-2 enriched
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6.3
[2]
[3]
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basal-like
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10.6
[2]
[3]
[49] array · 4 items
[0]
normal-like
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0.8
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[3]
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n.a.
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43.6
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100
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The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.
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CNJ3 mRNA expression levels as determined by RNAseq (n = 647). (B) Representative RNA in situ hy
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sly showed superiority of ISH over classical immunohistochemistry regarding sensitivity and specificity [18].
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2). Cell culture The breast cancer cell line MCF-7 (ATCC; Manassas, VA, USA; #HTB-22™) was grow
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l/L sodium pyruvate (Sigma Aldrich; #S8636). MCF-7 cells stably overexpressing KCNJ3 were produ
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:27835900", "kind": "science-record", "revision": 8, "content_hash": "sha256:aeffdc256d077385940a76bad824ed3d0872749afa0cb7a70c63766f03c0b4ca", "created_at": "2026-11-01T15:40:21Z", "updated_at": "2026-11-01T21:59:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "KCNJ3 is a new independent prognostic marker for estrogen receptor positive breast cancer patients.", "doi": "10.18632/oncotarget.13224", "pmid": "27835900", "authors": ["Sarah Kammerer", "Armin Sokolowski", "Hubert Hackl", "Dieter Platzer", "Stephan Wenzel Jahn", "Amin El-Heliebi", "Daniela Schwarzenbacher", "Verena Stiegelbauer", "Martin Pichler", "Simin Rezania", "Heidelinde Fiegl", "Florentia Peintinger", "Peter Regitnig", "Gerald Hoefler", "Wolfgang Schreibmayer", "Thomas Bauernhofer"], "journal": "Oncotarget", "year": 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 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.", "claims": [{"id": "claim-method", "statement": "A time-independent Cox-proportional hazard approach was applied for univariate and multivariate survival analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27835900", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "A time-independent Cox-proportional hazard approach was applied for univariate and multivariate survival analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:27835900", "locator": "sections[9] \"Gene expression data from the cancer genome atlas\" paragraph 2", "quote": "The gene expression levels (RNAseq V2 level 3 data) of 950 invasive breast carcinoma samples and of 105 samples from corresponding healthy tissues were downloaded from the The Cancer Genome Atlas (TCGA) data portal (https://tcga-data.nci.nih.gov) and the upper quartile normalized counts from the RSEM pipeline were used."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In ER-positive breast cancer patients, high KCNJ3 expression is associated with worse overall and disease-free survival, with KCNJ3 serving as an independent prognostic factor.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:27835900", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}, {"asset": "source:pmid:27835900", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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)."}, {"asset": "source:pmid:27835900", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "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."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "In ER-positive breast cancer patients, high KCNJ3 expression is associated with worse overall and disease-free survival, with KCNJ3 serving as an independent prognostic factor.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:27835900"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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