接受新辅助治疗的非小细胞肺癌患者的化疗敏感性和生存率取决于多药物外排转运蛋白的表达

Tijana Stankovic, J. Stojšić, M. Dragoj, Z. Milovanović, Z. Milošević, Vedrana P. Milinković, V. Škodrić-Trifunović, Ljiljana Denić-Marković, M. Pešić, Sonja Stojković Burić, N. Tanić, Jasna Banković
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引用次数: 1

摘要

非小细胞肺癌(NSCLC)患者的耐药外排转运蛋白、p -糖蛋白(P-gp/ ABCB1)、多药耐药相关蛋白(MRP1/ ABCC1)和乳腺癌耐药蛋白(BCRP/ ABCG2)。特别地,研究了它们作为NSCLC患者接受NACT化疗敏感性和预后的分子标志物的作用。为此,我们在两个独立的组中专门研究了这三种外排转运蛋白的mRNA和蛋白表达,每组由35名接受或未接受铂基NACT治疗的NSCLC患者组成。统计分析MDR外排转运蛋白表达的变化与NACT状态的关系,并评估其与患者生存的相关性。在NACT组中,MRP1阳性表达的样本频率显著降低,无论是否应用已知可诱导MRP1表达的铂类药物。另一方面,NACT组表达BCRP的肿瘤标本、BCRP和P-gp双阳性标本以及三阳性标本的发生率均有所增加。重要的是,缺乏P-gp表达的患者使用NACT的预后比不使用NACT的患者更好,而MRP1和BCRP的状态对两组患者的生存都没有影响。总的来说,我们发现NACT后MRP1的降低和BCRP表达的增加可以决定辅助治疗后NSCLC的化疗敏感性,而P-gp表达状态可以被认为是NSCLC患者从NACT治疗中获益的预后指标。
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Chemosensitivity and survival of non-small cell lung carcinoma patients receiving neoadjuvant therapy depend on the expression of multidrug efflux transporters
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. Impor-tantly, 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.
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