The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy

Anita Mangia, Lucia Caldarola, Stefania Dell’endice, Emanuela Scarpi, Luca Saragoni, Manlio Monti, Daniele Santini, Oronzo Brunetti, Giovanni Simone, Nicola Silvestris

Research output: Contribution to journalArticle

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Abstract

Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na+/H+exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8% versus 31.3% respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1a and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7% of patients with high nNHERF1 expression had a disease control rate, while 84.6% of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor.

Original languageEnglish
Article numberA1140
Pages (from-to)1140-1147
Number of pages8
JournalCancer Biology and Therapy
Volume16
Issue number8
DOIs
Publication statusPublished - 2015

Fingerprint

oxaliplatin
Epirubicin
Stomach Neoplasms
P-Glycoproteins
Drug Therapy
Neoplasms
P-Glycoprotein
Nuclear Proteins
Drug Resistance
Paraffin
Formaldehyde
Proteins
Multivariate Analysis
Immunohistochemistry
Staining and Labeling
Capecitabine

Keywords

  • Chemotherapy
  • Gastric cancer
  • Immunohistochemistry
  • Multi-drug resistance
  • NHERF1/EBP50
  • Predictive factor

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Molecular Medicine
  • Pharmacology

Cite this

The potential predictive role of nuclear NHERF1 expression in advanced gastric cancer patients treated with epirubicin/oxaliplatin/capecitabine first line chemotherapy. / Mangia, Anita; Caldarola, Lucia; Dell’endice, Stefania; Scarpi, Emanuela; Saragoni, Luca; Monti, Manlio; Santini, Daniele; Brunetti, Oronzo; Simone, Giovanni; Silvestris, Nicola.

In: Cancer Biology and Therapy, Vol. 16, No. 8, A1140, 2015, p. 1140-1147.

Research output: Contribution to journalArticle

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abstract = "Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na+/H+exchanger regulatory factor) is an important player in cancer progression for a number of solid malignancies, even if its role to develop drug resistance remains uncertain. Herein, we aimed to analyze the potential association between NHERF1 expression and P-gp, sorcin and HIF-1α MDR-related proteins in advanced GC patients treated with epirubicin/oxaliplatin/capecitabine (EOX) chemotherapy regimen, and its relation to response. Total number of 28 untreated patients were included into the study. Expression and subcellular localization of all proteins were assessed by immunohistochemistry on formalin-fixed paraffin embedded tumor samples. We did not found significant association between NHERF1 expression and the MDR-related proteins. A trend was observed between positive cytoplasmic NHERF1 (cNHERF1) expression and negative nuclear HIF-1α (nHIF-1α) expression (68.8{\%} versus 31.3{\%} respectively, P = 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1a and sorcin expression (P = 0.011; P = 0.002, respectively). Interestingly, nuclear NHERF1 (nNHERF1) staining was statistically associated with clinical response. In detail, 66.7{\%} of patients with high nNHERF1 expression had a disease control rate, while 84.6{\%} of subjects with negative nuclear expression of the protein showed progressive disease (P = 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P = 0.019). These results suggest that nuclear NHERF1 could be related to resistance to the EOX regimen in advanced GC patients, identifying this marker as a possible independent predictive factor.",
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AU - Dell’endice, Stefania

AU - Scarpi, Emanuela

AU - Saragoni, Luca

AU - Monti, Manlio

AU - Santini, Daniele

AU - Brunetti, Oronzo

AU - Simone, Giovanni

AU - Silvestris, Nicola

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