Integrin-Linked Kinase, Snail and Multidrug Resistance Protein 1: Three concordant players in the progression of non-small cell lung cancer

Background: Integrin Linked Kinase (ILK), Snail and Multidrug Resistance Protein 1 (MRP1) have been implicated in several cancers; however, their roles in non-small cell lung cancer (NSCLC) remain to be elucidated. Aim: Investigation of their expression in NSCLC tissue. Relationships among these proteins and their association with clinicopathological parameters were studied. Materials and methods: ILK, Snail and MRP1 expression were immunohistochemically assessed in 97 tumor tissues. Furthermore, western blot analysis for ILK, Snail and MRP1 in 6 cases of NSCLC was also performed. Results: ILK overexpression, positive Snail and MRP1 expression were found in 46.4%, 36.1% and 49.5% of tumors respectively. ILK expression was significantly correlated with tumor grade (p = 0.013), lymph node (LN) metastases (p = 0.001) and stage (p = 0.001). Positive Snail and MRP1 expression were significantly associated with LN metastasis (p = 0.004 and 0.022, respectively) and advanced stage disease (p = 0.018 and 0.024, respectively). MRP1 expression was significantly higher among adenocarcinoma cases compared to other types (p = 0.001). ILK over-expression was significantly associated with up-regulation of Snail and MRP1 (p < 0.001 both). Significant association was also, found between Snail and MRP1 expression (p = 0.005). Moreover, the co-expression of two markers or more was significantly associated with less differentiation (p = 0.011), advanced tumor status (p = 0.030), LN metastasis (p < 0.001) and advanced stage ( p < 0.001) disease. Western blot analysis validated immunohistochemical findings. Conclusion: ILK may have an important role in the progression of NSCLC, possibly through up-regulation of Snail and MRP1. ILK, Snail and MRP1 are important molecular markers for predicting carcinogenesis and progression of NSCLC. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University.