Kolwijck Eva, Zusterzeel Petra L M, Roelofs Hennie M J, Hendriks Jan C, Peters Wilbert H M, Massuger Leon F A G
Department of Obstetrics and Gynecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2176-81. doi: 10.1158/1055-9965.EPI-09-0098.
Detoxification enzymes, especially glutathione S-transferase P1-1 (GSTP1-1), have been implicated in resistance to platinum-based chemotherapy. We studied GSTP1-1 levels in ovarian cyst fluid (oCF), obtained during surgery before chemotherapy, of patients with epithelial ovarian cancer and clinical outcomes were correlated. GSTP1-1 was determined by ELISA in oCF of 56 patients with epithelial ovarian cancer and 109 noncancer controls (21 borderline and 88 benign ovarian tumors). Differences in median GSTP1-1 between clinicopathologic subgroups were studied using Mann-Whitney U and Kruskal Wallis tests. Differences in disease-free (DFS) and overall survival (OS) between groups were analyzed by applying Kaplan-Meyer estimates and log-rank tests. Univariate and multivariate analysis were done using Cox proportional hazard model. Significantly higher levels of GSTP1-1 were found in the oCF of malignant (median, 383; range, 10-32,695 ng/mL) compared with benign (median, 20; range, 0-1,128 ng/mL) ovarian tumors (P < 0.01). Significantly higher GSTP1-1 levels were found in patients with advanced International Federation of Gynaecologists and Obstetricians stage (P = 0.01), high-grade tumors (P = 0.44), and/or high levels of preoperative CA 125 (P = 0.01). Of patients who received chemotherapy (stage, >or=Ic; n = 30), high GSTP1-1 levels were significantly associated with a poor DFS and OS (log-rank P = 0.047 and P = 0.033, respectively). International Federation of Gynaecologists and Obstetricians stage was the only independent predictor for DFS. GSTP1-1 was the only independent predictor for OS.
解毒酶，尤其是谷胱甘肽S-转移酶P1-1（GSTP1-1），与铂类化疗耐药有关。我们研究了上皮性卵巢癌患者化疗前手术获取的卵巢囊肿液（oCF）中的GSTP1-1水平，并将其与临床结局相关联。通过酶联免疫吸附测定（ELISA）法测定了56例上皮性卵巢癌患者及109例非癌症对照者（21例交界性和88例良性卵巢肿瘤）oCF中的GSTP1-1。使用曼-惠特尼U检验和克鲁斯卡尔-沃利斯检验研究了临床病理亚组之间GSTP1-1中位数的差异。采用Kaplan-Meier估计法和对数秩检验分析了各组之间无病生存期（DFS）和总生存期（OS）的差异。使用Cox比例风险模型进行单因素和多因素分析。与良性卵巢肿瘤（中位数为20；范围为0-1128 ng/mL）相比，恶性卵巢肿瘤oCF中GSTP1-1水平显著更高（中位数为383；范围为10-32695 ng/mL）（P<0.01）。国际妇产科联盟（FIGO）晚期患者、高级别肿瘤患者和/或术前CA 125水平高的患者中GSTP1-1水平显著更高（P = 0.01、P = 0.44、P = 0.01）。在接受化疗的患者（分期≥Ic；n = 30）中，GSTP1-1水平高与DFS和OS较差显著相关（对数秩检验P分别为0.047和0.033）。FIGO分期是DFS的唯一独立预测因素。GSTP1-1是OS的唯一独立预测因素。
