Research On Expressions Of ABCC10 And Their Correlation With Chemoresistance In Non-small Cell Lung Cancer

Lung cancer is one of the most popular malignant tumors. The mortality of lung cancer is the first in all tumors. About 1 million people die of lung cancer all over the world every year. The people who die of lung cancer accounts for one sixth of those who die of all kinds of tumors. Non-small cell lung cancer (NSCLC, squamous cell carcinoma, adenocarcinoma and large cell carcinoma) is the most common type of lung cancer. Chemotherapy plays a key role in NSCLC. However, it often failed because of multi-drug resistence (MDR). It has been reported that the ABC membrane transporters play an important role in the mechanism of MDR. ABCC10 is the recent member of ABC superfamily (ATP-binding cassette transporter superfamily). Researchs in vitro revealed that the high expression of ABCC10 maybe play a role in the drug resistance in NSCLC. However, the expressions of ABCC10 in human tumors, especially in NSCLC, and their correlation with chemosensitivity of NSCLC tissues have not been reported.ObjectiveTo detect the expression of ABCC10 in non-small cell lung cancer and compare its clinical significance and its correlation with chemosensitivity.MethodsThe expressions of ABCC10 in 75 untreated tumor samples and their corresponding normal tissues were detected by immunohistochemistry and RT-PCR, respectively. The differences of the ABCC10 expressions between tumor tissues and normal tissues were analyzed, as well as in different pathological grades and TNM stages. Furthermore, the chemosensitivities of NSCLC tissues to 10 anti-cancer drugs, including cyclophoaphamide, 5-fluorouracil, gemcitabine, adriamycin, docetaxek, paclitaxel, vinorelbine, vincristine, cisplatin and carboplatin, were tested by using MTT method in 75 cases. Finally the correlation of ABCC10 expressions with the chemoresistance of tumor cases was analyzed statistically.ResultsThe results of immunohistochemistry revealed that ABCC10 was mainly located in cell membrane and cytoplasm. Significant differences of ABCC10 expressions were observed between tumor tissues and their corresponding normal tissues( P<0.01). Among pathological grades and TNM stages in squamous cell carcinoma and adenocarcinoma, the expressions of ABCC10 were markedly different( P<0.05). The results of RT-PCR revealed that the expressions of ABCC10 in tumor tissues and their corresponding normal tissues were 0.3821±0.0212, 0.0419±0.0061, respectively, and there were significant differences between the two groups(P<0.01). There was high correlation between the expressions detected by immunohistochemistry and RT-PCR in tumor tissues(P<0.01, rs=0.69). It has been shown that there were remarkable correlations(P < 0.01) between the expressions of ABCC10 detected by immunohistochemistry and the chemoresistance of the tumor tissues to docetaxel, paclitaxel, vinorelbine, vincristine, and cisplatin, with correlation coefficients being 0.674, 0.633, 0.610, 0.565 and 0.532. It has also been indicted that the expressions of ABCC10 detected by RT-PCR had significant correlations to the chemoresistance of the tumor tissues to paclitaxel, vinorelbine and cisplatin, with correlation coefficient being 0.553, 0.495 and 0.421.ConclusionsABCC10 is overexpressed in NSCLC. The expression rate in NSCLC is correlated to pathological grades and TNM stages. The chemoresistance of NSCLC is probably correlated with the ABCC10 expression.