An
actin-binding protein filamin A connects the actin filament network to cell membrane receptors, and acts as a scaffold for various signaling pathways related to
cancer growth and progression. Recently, it has been reported that
filamin A is required for efficient regulation of early stages of DNA repair process. Moreover, some in vitro studies showed that the overexpression of
filamin A determines resistance to various cytotoxic drugs, including
cisplatin. We aimed to analyse the expression of
filamin A protein in resected NSCLC (
Non Small Cell Lung Cancer) specimens, to investigate the association of the level of
filamin A protein expression and other clinicopathological features, and possible relationship between the expression of
filamin A and survival outcome in NSCLC patients, treated with
platinum-based
combination chemotherapy. We performed
filamin A protein immunohistochemistry on
formalin-fixed and
paraffin-embedded (FFPE) tissue sections from 135 NSCLC patients, using EP2405Y antibody against C-terminus of
filamin A. Cytoplasmic, membranous and nuclear positivity of
filamin A was evaluated semi-quantitatively and correlated with available clinicopathological data. Patients were divided into two groups for survival analysis (I group - patients treated with adjuvant
platinum-based
chemotherapy, II group - patients with surgical treatment only). We found significant positive correlation between
filamin A protein expression and NSCLC stage (r=0.249; p<0,05), presence of lymph node (N)(r=0.205; p<0,05) and distant
metastases (M) (r=0.332; P<0.01). Increased
filamin A protein expression was significantly related with poor survival outcomes in patients with adjuvant
platinum-based
chemotherapy: OS (HR=1.005, 95%CI[1.000;1.010], p=0.037), DFS (HR=1.004, 95%CI [1.001:1.008], p=0,017). Multivariate Cox proportional hazards regression analysis also showed that overexpression of
filamin A represents an independent risk factor for disease relapse, in addition to
tumor size, stage, and
metastases status (HR=1.723, 95%CI [1.021:2.909], p<0.05). Thus,
filamin A expression might be a new prognostic marker in patients with NSCLC.