Naniwa J, Kigawa J, Kanamori Y, Itamochi H, Oishi T, Shimada M, Shimogai R, Kawaguchi W, Sato S, Terakawa N
Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishimachi, Yonago 683-8504, Japan.
Int J Gynecol Cancer. 2007 Jan-Feb;17(1):76-82. doi: 10.1111/j.1525-1438.2006.00752.x.
We conducted the present study to investigate whether and how chemosensitivity can be determined by means of genetic diagnosis using drug-resistance genes in patients with epithelial ovarian cancer. A total of 75 patients who had epithelial ovarian cancer with measurable lesions were entered into this study. Thirty-three patients received first-line chemotherapy, consisting of paclitaxel and carboplatin (TJ). Forty-two patients received second-line chemotherapy, 22 received EP therapy consisting of etoposide and cisplatin (CDDP), and 20 received irinotecan (CPT-11) and CDDP (CPT-11/CDDP) therapy. Tumor samples were obtained before chemotherapy. MessengerRNA expressions of the multidrug-resistance (MDR)-1 gene, MDR-associated protein-1 (MRP-1), topoisomerase (topo) I, and topo IIalpha were measured by real-time reverse transcription-polymerase chain reaction. The cutoff values of each gene were determined by the receiver operating characteristic curve. MDR-1 expression was significantly higher in patients who did not respond to TJ therapy. The expression of topo IIalpha was significantly higher in patients who did respond to EP therapy. The expression of topo I was significantly higher in patients who did respond to CPT-11/CDDP. MRP-1 expression did not differ between responders and nonresponders in all regimens. The cutoff value was 80 for MDR-1, 90 for topo IIalpha, and 200 for topo I. Next, to evaluate genetic diagnosis, 31 patients were newly added. The accuracy of this genetic diagnosis for chemosensitivity was 85.7% for TJ, 77.8% for EP, and 100.0% for CPT-11/CDDP therapy. The present study suggests that genetic diagnosis may be useful to determine chemosensitivity in patients with epithelial ovarian cancer.
我们开展了本研究，以调查上皮性卵巢癌患者是否以及如何通过使用耐药基因进行基因诊断来确定化疗敏感性。共有75例患有可测量病灶的上皮性卵巢癌患者纳入本研究。33例患者接受了一线化疗，方案为紫杉醇联合卡铂（TJ）。42例患者接受二线化疗，22例接受依托泊苷联合顺铂（CDDP）的EP方案治疗，20例接受伊立替康（CPT-11）联合CDDP（CPT-11/CDDP）方案治疗。化疗前获取肿瘤样本。通过实时逆转录聚合酶链反应测量多药耐药（MDR）-1基因、多药耐药相关蛋白-1（MRP-1）、拓扑异构酶（topo）I和topo IIα的信使核糖核酸表达。每个基因的临界值通过受试者工作特征曲线确定。对TJ治疗无反应的患者中MDR-1表达显著更高。对EP治疗有反应的患者中topo IIα表达显著更高。对CPT-11/CDDP有反应的患者中topo I表达显著更高。在所有治疗方案中，MRP-1表达在有反应者和无反应者之间无差异。MDR-1的临界值为80，topo IIα为90，topo I为200。接下来，为评估基因诊断，新增加了31例患者。这种基因诊断对化疗敏感性的准确率在TJ方案中为85.7%，EP方案中为77.8%，CPT-11/CDDP方案中为100.0%。本研究表明，基因诊断可能有助于确定上皮性卵巢癌患者的化疗敏感性。
