The Expression Of SLC22A18in Non-small Cell Lung Cancer And Their Correlation With Drug-resistance

Background：Lung cancer is one of the most common malignancy tumors in the clinic,and its morbidity and mortality rank the first in all the kinds of cancers in theworld, of which non-small cell lung cancer(NSCLC) accounts for about80percent. Chemotherapy is the primary means of comprehensive treatment toNSCLC, but its efficiency is only14to40percent. Studies have shown that themulti-drug resistance (MDR) is the main reason for the failure of chemotherapyin lung cancer, and the increased activity of drug transporters plays an importantrole in MDR. SLC22A18is a new paternal imprinted gene found in recent years,and the structure of SLC22A18protein is similar to that of transmembranetransporter. What the expression of SLC22A18in bacteria is associated withdrug resistance has been confirmed, but in human tumors, especially in NSCLCtissues, the expression of SLC22A18and their correlation with drug resistance have not been reported.Objective：To investigate the expression of SLC22A18protein in NSCLC and analyzerelationship of SLC22A18expression in these tissues with different histologicaltypes, pathological grades and TNM stages; to test the chemosensitivity of sametissues, and explore the correlation of the chemosensitivity with SLC22A18expression in NSCLC.Methods：The expression of SLC22A18was detected by immunohistochemistrymethod and RT-PCR in96cases with NSCLC and corresponding normal lungtissues.The chemosensitivity of the same cases to cyclophosphamide,5-fluorouracil, gemcitabine, doxorubicin, paclitaxel, vinorelbine docetaxel,cisplatin and carboplatin were assayed by MTT method, and the correlation ofthe chemoresistance with expression of SLC22A18in NSCLC was analyzed bystatistics. Statistics analysis was carried out with SPSS17.0statistics software.Results：1.The results of immunohistochemistry showed that SLC22A18wasmainly localized in cell membrane and cytoplasm. The expression rate ofSLC22A18in NSCLC was higher than that of the corresponding normaltissue(P=0.000). The expression rate of SLC22A18in lung adenocarcinoma washigher than that in lung squamous cell carcinoma(P=0.015). Significantdifferences of the expression rates were observed among histological grades andTNM stages respectively in both lung squamous cell carcinoma and lungadenocarcinoma(P<0.05).2.The results of RT-PCR showed that the expression level of SLC22A18in NSCLC was higher than that in their corresponding normal tissues(P=0.000).There was significant difference of the SLC22A18expression level betweenlung squamous cell carcinoma and lung adenocarcinoma(P=0.000). Meanwhile,differences of the expression level were found among histological grades andTNM stages in the two types of lung cancer(P<0.05).There was high correlationbetween the results detected by immunohistochemistry and RT-PCR(P=0.000,rs=0.749).3.Tumor samples displayed lower chemosensitivity to gemcitabine,doxorubicin, paclitaxel, vinorelbine, docetaxel and cisplatin detected by MTTmethod in lung adenocarcinoma than that in lung squamous cellcarcinoma(P<0.05).The SLC22A18expression rate detected byimmunohistochemistry was correlated with the chemosensitivity of the tumortissues to paclitaxel, vinorelbine, docetaxel and cisplatin(P<0.05, rs=－0.585,－0.571,－0.633,－0.643). It had also been indicted that the expression leveldetected by RT-PCR was significant correlation to the chemosensitivity of thetumor tissues to paclitaxel, docetaxel, cisplatin and carboplatin(P<0.05, rs=－0.611,－0.608,－0.640,－0.507).Conclusions：The SLC22A18is overexpressed in NSCLC, and the expression in NSCLCis higher than that in their corresponding normal tissues.The expression ofSLC22A18is correlated to histological types, pathological grades and TNMstages. The chemoresistance in NSCLC is probably correlated with theSLC22A18expression.