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

Abstract

Cellular resistance in advanced gastric cancer (GC) might be related to function of multidrug resistance (MDR) proteins. The adaptor protein NHERF1 (Na C /H C 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-1a 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-1a (nHIF-1a) expression (68.8% versus 31.3% respectively, P D 0.054). However, cytoplasmic P-gp (cP-gp) expression was positively correlated with both cHIF-1a and sorcin expression (P D 0.011; P D 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 D 0.009). Multivariate analysis confirmed a significant correlation between nNHERF1 and clinical response (OR 0.06, P D 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.

Targeting P‐glycoprotein and SORCIN: Dihydromyricetin strengthens anti‐proliferative efficiency of adriamycin via MAPK/ERK and Ca2+‐mediated apoptosis pathways in MCF‐7/ADR and K562/ADR

“…SORCIN, soluble resistance‐related calcium‐binding protein, is a penta‐EF hand Ca 2+ binding protein implicated in regulation of intracellular calcium homeostasis (Colotti et al, ). SORCIN is highly expressed in some mammalian normal tissues such as heart (Suarez et al, ) and brain (Kim, Lee, Kim, Kwon, & Chun, ), and overexpresses in various cancer multidrug‐resistance cells (Mangia et al, ; Meyers, Schneider, Spengler, Chang, & Biedler, ). SORCIN participates in the formation of drug resistance in tumoral cells (Gao, Li, Liu, Gao, & Zhao, ).…”

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

“…The NHERF1 protein is physiologically expressed at the apical membrane of polarized epithelial cells and it is a major component of signalling complexes [ 7 , 8 ]. Increased NHERF1 expression has been reported in a variety of human malignant tissues [ 3 , 9 - 14 ]. The most extensive analyses of the role of NHERF1 in cancer development have been performed for BC [ 7 , 15 - 17 ].…”

Role of miR-27a, miR-181a and miR-20b in gastric cancer hypoxia-induced chemoresistance

“…40 The primary antibody was mouse monoclonal anti-HIPK2 (ab57328; Abcam; 1:300 dilution). Human gastric tissues were used as positive control and the primary antibody was omitted and replaced by PBS pH7.6 for negative control.…”