Overexpression of filamin-A protein is associated with aggressive phenotype and poor survival outcomes in NSCLC patients treated with platinum-based combination chemotherapy.

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.

Quadriplex model enhances urine-based detection of prostate cancer.

BACKGROUND: The major advantages of urine-based assays are their non-invasive character and ability to monitor prostate cancer (CaP) with heterogeneous foci. While the test for the prostate cancer antigen 3 (PCA3) is commercially available, the aim of our research was to test other putative urine markers in multiplex settings (AMACR (α-methylacyl-CoA racemase), EZH2 (enhancer of zeste homolog 2), GOLM1 (golgi membrane protein 1), MSMB (microseminoprotein, ß), SPINK1 (serine peptidase inhibitor) and TRPM8 (transient receptor potential cation channel, subfamily M, member 8)). METHODS: Expression of the candidate biomarkers was studied in sedimented urine using quantitative reverse transcriptase polymerase chain reaction in two sets of patients with and without restriction on serum PSA levels. RESULTS: We confirmed that PCA3 is an independent predictor of cancer in the patients without restriction of serum PSA values (set 1, n=176, PSA=0.1-587 ng ml(-1)). However, AMACR was the only parameter that differentiated CaP from non-CaP patients with serum PSA between 3 and 15 ng ml(-1) (set 2, n=104). The area under curve (AUC) for this gene was 0.645 with both sensitivity and specificity at 65%. Further improvement was achieved by multivariate logistic regression analysis, which identified novel duplex (TRPM8 and MSMB), triplex (plus AMACR) and quadriplex (plus PCA3) models for the detection of early CaPs (AUC=0.665, 0.726 and 0.741, respectively). CONCLUSIONS: Novel quadriplex test could be implemented as an adjunct to serum PSA or urine PCA3 and this could improve decision making for diagnostics in the case of 'PSA dilemma' patients.