15P Change of mTOR, p6, NBR1 and LC3A/B-I/II in A549 cells treated with graphene oxides

Abstract

Background: Measuring levels of ligands in peripheral blood representing systemic circulation and in blood isolated from tumour vascular bed accompanied by evaluation of binding receptor expression in tumour tissue gives insight into cancerogenesis. We have incorporated this research strategy into surgical practice to investigate the role of CXC chemokines as potential biomarkers of lung cancer. Methods: The study recruited 40 patients (mean age 62±10.4) with primary NSCLC ranging from stage IA to IIB undergoing anatomical pulmonary resection between June 2010 and October 2014. Blood samples from peripheral vein and from pulmonary vein draining tumour vascular bed were collected at the time of surgery. Levels of CXC chemokine ligands (CXCL) potentially involved in cancerogenesis – CXCL1, CXCL4, CXCL5, CXCL6, CXCL7, CXCL8, CXCL9, CXCL10, CXCL11 and CXCL12 were measured using ELISA. CXCL gradients were calculated. Corresponding CXC chemokine receptor (CXCR) expression – CXCR1, CXCR2, CXCR3 and CXCR4 was evaluated in resected tumour by immunohistochemistry and analysed semiquantitatively (expression intensity scale 0–3). Prognostic value of CXCL levels and CXCR expression was assessed evaluating relapse time. Paired two-tailed t-test was used to compare CXCL levels and Pearson test was used to assess statistical relationship between CXCL levels and CXCR expression. Results: Statistically significant difference between circulating CXC levels was found for CXCL4 (p < 0.001), CXCL5 (p < 0.05), CXCL7 (p < 0.001). Moderate statistically significant correlation was found between CXCL10, CXCL11 gradient and stromal expression of CXCR3. CXCL1, CXCL4 and CXCL10 gradients correlated with relapse (r = 0.38, r = 0.39, r = 0.35, p < 0.05). CXCR2 expression in tumour tissue correlated with relapse (r = 0.44, p < 0.05) and mortality (r = 0.45, p < 0.05). Conclusions: Our approach has facilitated identifying chemokine ligands and receptors potentially involved in NSCLC tumour metabolism and improved understanding of a complex and variable background of proteomic profile in lung cancer leading to biomarker discovery. Legal entity responsible for the study: Pauls Stradins Clinical University Hospital Funding: Pauls Stradins Clinical University Hospital Disclosure: All authors have declared no conflicts of interest.