Chemosensitivity and survival of non-small cell lung carcinoma patients receiving neoadjuvant therapy depend on the expression of multidrug efflux transporters

Abstract

The current study aimed to evaluate the impact of neoadjuvant chemotherapy (NACT) on the expression of three major multidrug resistance efflux transporters, P-glycoprotein (P-gp/ABCB1), multidrug resistance associated protein (MRP1/ABCC1) and breast cancer resistance protein (BCRP/ABCG2) in non-small cell lung carcinoma (NSCLC) patients. Particularly, their role as molecular markers of chemosensitivity and prognosis of NSCLC patients receiving NACT was investigated. To that end, we specifically studied mRNA and protein expression of these three efflux transporters in two independent groups, each consisting of 35 NSCLC patients who did or did not receive platinum-based NACT. Alterations in the expression of MDR efflux transporters were statistically analyzed in relation to NACT status, and their associations were evaluated regarding patients’ survival. The frequency of samples with positive MRP1 expression was significantly decreased in the NACT group, regardless of the applied platinum drugs which are known to induce MRP1 expression. On the other hand, the incidence of BCRP expressing tumor specimens, doubly positive BCRP and P-gp as well as triple positive samples increased in the NACT group. Importantly, patients lacking P-gp expression had more favorable prognosis with NACT than without NACT, whereas the status of MRP1 and BCRP did not influence the patients’ survival in both investigated groups. Collectively, we show that decreased MRP1 and increased BCRP expression after NACT could determine the chemosensitivity of NSCLC following adjuvant therapy, whereas P-gp expression status could be considered a prognostic marker for NSCLC patients who can benefit from NACT treatment.