NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients

Anita Mangia, Emanuela Scarpi, Giulia Partipilo, Laura Schirosi, Giuseppina Opinto, Francesco Giotta, Giovanni Simone

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 languageEnglish
Pages (from-to)65730-65742
Number of pages13
JournalOncotarget
Volume8
Issue number39
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Biomarkers
Breast Neoplasms
Survival
BRCA1 Protein
Survival Analysis
Immunohistochemistry
sodium-hydrogen exchanger regulatory factor
Neoplasms
Proteins
Therapeutics

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 journalArticle

@article{27f285fc503246dd94fac8d9d38badce,
title = "NHERF1 together with PARP1 and BRCA1 expression as a new potential biomarker to stratify breast cancer patients",
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.",
keywords = "BRCA1, Breast cancer, Immunohistochemistry, Na/H exchanger regulatory factor 1 (NHERF1), PARP1",
author = "Anita Mangia and Emanuela Scarpi and Giulia Partipilo and Laura Schirosi and Giuseppina Opinto and Francesco Giotta and Giovanni Simone",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/oncotarget.19444",
language = "English",
volume = "8",
pages = "65730--65742",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "39",

}

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

VL - 8

SP - 65730

EP - 65742

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 39

ER -