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.