Multidrug resistance-associated biomarkers PGP, GST-π, Topo-II and LRP as prognostic factors in primary ovarian carcinoma

Abstract

This study aims to investigate the expression of P-glycoprotein (PGP), glutathione S-transferase pi (GST-pi), DNA topoisomerase II (Topo-II) and lung resistance-related protein (LRP) in ovarian carcinoma, thus providing better chemotherapy choice and post-operative prognosis for ovarian carcinoma patients. A total of 80 primary ovarian carcinoma, 16 benign ovarian epithelial neoplasm, and 12 normal ovarian tissue samples were collected. Immunohistochemistry was used to detect the expression of PGP, GST-pi, Topo-II and LRP, and the results were analysed by correlation with clinicopathological parameters. Positive expression rates of PGP, GST-pi, Topo-II and LRP in patients with ovarian carcinoma (57.5%, 58.8%, 76.3% and 73.8%, respectively) were all higher than those found in normal and benign tissue (P<0.05). In clinical stages I/II vs. III/IV, the expression rates of PGP, GST-pi, Topo-II and LRP were 40.7% vs. 66% (P<0.05), 40.7% vs. 67.9% (P<0.05), 66.7% vs. 81.1% (P>0.05) and 55.6% vs. 83.0% (P<0.05), respectively. Carcinoma differentiation ranged from well to poor, and expression levels of each marker were as follows: PGP, 57.9%, 62.1% and 53.1% (P>0.05); GST-pi, 36.8%, 55.2% and 75.0% (P<0.05); Topo-II, 52.6%, 79.3% and 87.5% (P<0.05); and LRP, 84.2%, 69.0% and 71.9% (P>0.05). Ovarian carcinoma patients with PGP-, GST-pi-, Topo-II- and LRP-positive expression had a shorter median survival time than those who were negative for these markers (PGP: 36 months vs. 48 months [P=0.0017]; GST-pi: 36 months vs. 41 months [P=0.0103]; Topo-II: 37 months vs. 39 months [P=0.3811]; LRP: 37 months vs. 55 months [P=0.002]). COX regression analysis demonstrated that the clinical stage of the tumour, and the expression of PGP, GST-pi or LRP, may influence patient survival time after surgery. The relative death risk for patients with clinical stage III/IV tumours increased 9.46-fold compared to those with stage I/II tumours. The relative death risk in the PGP-, GST-pi- and LRP-positive groups increased by 2.049-, 2.452- or 2.609-fold, respectively, compared with the corresponding negative groups. PGP, GST-pi, Topo-II and LRP are all expressed in primary ovarian carcinoma, indicating the presence of multidrug resistance in this disease. Combined evaluation of PGP, GST-pi, Topo-II and LRP expression may enable better chemotherapeutic choice and provide an accurate prognosis for ovarian carcinoma patients.

Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs

“…P-gp is the best-known and principal mediator of MDR. P-gp, which is encoded by MDR1, is involved in pumping chemotherapy drugs from the inside to the outside of tumor cells, and in preventing intracellular accumulation of these drugs (20,24). MRP1 functions similarly to MDR1 in reducing tumor sensitivity to chemotherapy, and it can recognize and pump out chemotherapy drugs bound to glutathione in tumor cells.…”

Prognostic Value and Implication for Chemotherapy Treatment of ABCB1 in Epithelial Ovarian Cancer: A Meta-Analysis

“…Although a great number of studies evaluated the effect of ABCB1 on EOC patients, the association between ABCB1 and EOC prognosis was still under debate. While certain amount of studies reported that high ABCB1 could predict unfavorable prognosis [23,28,30,31,34,35], quite a few did not find any significant association between ABCB1 and survival in patients with EOC [18,27,32]. The possible reasons for these inconsistent results might include (i) heterogeneities of the basic characteristics of the studies such as sample sizes, EOC subtypes, clinical stage, and populations, (ii) different intervention such as residual disease after surgery, time point of ABCB1 measurement and (iii) different methodology such as detection methods and procedures.…”

Significance of MDR-related proteins in the postoperative individualized chemotherapy of gastric cancer

“…[7,8] It had been confirmed that MRP and GST-π overexpression, and decreased expression of ToPo II were important mechanisms-mediated multidrug resistance. [9] So, we carried out the study of multidrug resistance (MDR) gene related proteins in post-operative individualized treatment of gastric cancer.…”