Abstract
It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs). Herein, we show that nuclear NHERF1 (nNHERF1) expression was significantly associated with nuclear BRCA1 (nBRCA1) expression (p=0.0008), and an association was also found between nuclear PARP1 (nPARP1) and nBRCA1 (p < 0.0001). Cytoplasmic NHERF1 (cNHERF1) was correlated to nPARP1 (p < 0.0001). Survival analyses showed that the patients with positive nPARP1 and nNHERF1 tended toward a shorter 5-year overall survival (OS) (p=0.057). In TNBCs, the association between nBRCA1 and nPARP1 was maintained (p < 0.0001), and an association between nNHERF1 and nPARP1 was observed (p=0.010). Univariate analysis revealed that TNBCs with positive cNHERF1 and nPARP1 had a shorter 5-year OS (p=0.048). Our data suggest that NHERF1 could be a new potential biomarker in combination with PARP1 and BRCA1 expression to stratify BC patients. In particular, in TNBCs, cNHERF1 associated with nPARP1 expression identified a patient subgroup with a shorter survival, for whom it may be useful to develop novel therapeutic strategies.
| Original language | English |
|---|---|
| Pages (from-to) | 65730-65742 |
| Number of pages | 13 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 39 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- BRCA1
- Breast cancer
- Immunohistochemistry
- Na/H exchanger regulatory factor 1 (NHERF1)
- PARP1
ASJC Scopus subject areas
- Oncology
Cite this
NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients. / Mangia, Anita; Scarpi, Emanuela; Partipilo, Giulia; Schirosi, Laura; Opinto, Giuseppina; Giotta, Francesco; Simone, Giovanni.
In: Oncotarget, Vol. 8, No. 39, 01.01.2017, p. 65730-65742.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients
AU - Mangia, Anita
AU - Scarpi, Emanuela
AU - Partipilo, Giulia
AU - Schirosi, Laura
AU - Opinto, Giuseppina
AU - Giotta, Francesco
AU - Simone, Giovanni
PY - 2017/1/1
Y1 - 2017/1/1
N2 - It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs). Herein, we show that nuclear NHERF1 (nNHERF1) expression was significantly associated with nuclear BRCA1 (nBRCA1) expression (p=0.0008), and an association was also found between nuclear PARP1 (nPARP1) and nBRCA1 (p < 0.0001). Cytoplasmic NHERF1 (cNHERF1) was correlated to nPARP1 (p < 0.0001). Survival analyses showed that the patients with positive nPARP1 and nNHERF1 tended toward a shorter 5-year overall survival (OS) (p=0.057). In TNBCs, the association between nBRCA1 and nPARP1 was maintained (p < 0.0001), and an association between nNHERF1 and nPARP1 was observed (p=0.010). Univariate analysis revealed that TNBCs with positive cNHERF1 and nPARP1 had a shorter 5-year OS (p=0.048). Our data suggest that NHERF1 could be a new potential biomarker in combination with PARP1 and BRCA1 expression to stratify BC patients. In particular, in TNBCs, cNHERF1 associated with nPARP1 expression identified a patient subgroup with a shorter survival, for whom it may be useful to develop novel therapeutic strategies.
AB - It has been recognized that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) in breast cancer (BC) acts as a tumor suppressor or as an oncogenic protein, depending on its subcellular localization. This study aims to correlate NHERF1 expression to BRCA1 and PARP1 proteins, to investigate their relationship, and their biological and clinical significance. Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs). Herein, we show that nuclear NHERF1 (nNHERF1) expression was significantly associated with nuclear BRCA1 (nBRCA1) expression (p=0.0008), and an association was also found between nuclear PARP1 (nPARP1) and nBRCA1 (p < 0.0001). Cytoplasmic NHERF1 (cNHERF1) was correlated to nPARP1 (p < 0.0001). Survival analyses showed that the patients with positive nPARP1 and nNHERF1 tended toward a shorter 5-year overall survival (OS) (p=0.057). In TNBCs, the association between nBRCA1 and nPARP1 was maintained (p < 0.0001), and an association between nNHERF1 and nPARP1 was observed (p=0.010). Univariate analysis revealed that TNBCs with positive cNHERF1 and nPARP1 had a shorter 5-year OS (p=0.048). Our data suggest that NHERF1 could be a new potential biomarker in combination with PARP1 and BRCA1 expression to stratify BC patients. In particular, in TNBCs, cNHERF1 associated with nPARP1 expression identified a patient subgroup with a shorter survival, for whom it may be useful to develop novel therapeutic strategies.
KW - BRCA1
KW - Breast cancer
KW - Immunohistochemistry
KW - Na/H exchanger regulatory factor 1 (NHERF1)
KW - PARP1
UR - http://www.scopus.com/inward/record.url?scp=85030126621&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85030126621&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.19444
DO - 10.18632/oncotarget.19444
M3 - Article
AN - SCOPUS:85030126621
VL - 8
SP - 65730
EP - 65742
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 39
ER -