Su Dan, Smith Stephanie M, Preti Mario, Schwartz Peter, Rutherford Thomas J, Menato Guido, Danese Saverio, Ma Shenglin, Yu Herbert, Katsaros Dionyssios
Research Institute, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Cancer. 2009 Jun 1;115(11):2453-63. doi: 10.1002/cncr.24282.
Paclitaxel interacts with microtubules to exert therapeutic effects. Molecules that affect microtubule activity, such as betaIII-tubulin and stathmin, may interfere with the treatment. In this study, the authors analyzed betaIII-tubulin and stathmin expression in ovarian tumors and examined their associations with treatment response and patient survival.
The study included 178 patients with epithelial ovarian cancer who underwent cytoreductive surgery followed by platinum-based chemotherapy; of these patients, 75 also received paclitaxel. Fresh tumor samples that were collected at surgery were analyzed for messenger RNA expression of betaIII-tubulin and stathmin using real-time polymerase chain reaction analysis. Associations of these molecules with treatment response, disease progression, and overall survival were evaluated.
High stathmin expression was associated with worse disease progression-free and overall survival compared with low stathmin expression. This association was independent of patient age, disease stage, tumor grade, histology, and residual tumor size and was observed in patients who received platinum plus paclitaxel, but not in patients who received platinum without paclitaxel, suggesting that stathmin expression in tumor tissue may interfere with paclitaxel treatment. Similar effects were not observed for betaIII-tubulin, although high betaIII-tubulin expression was associated with disease progression among patients who received platinum without paclitaxel. No associations were observed between treatment response and tubulin or stathmin expression. Expression levels of betaIII-tubulin and stathmin were correlated significantly.
High stathmin expression predicted an unfavorable prognosis in patients with ovarian cancer who received paclitaxel and platinum chemotherapy. This finding supports the possibility that stathmin may interfere with paclitaxel treatment, leading to a poor prognosis for patients with ovarian cancer.
紫杉醇通过与微管相互作用发挥治疗作用。影响微管活性的分子,如βIII-微管蛋白和Stathmin,可能会干扰治疗效果。在本研究中,作者分析了卵巢肿瘤中βIII-微管蛋白和Stathmin的表达情况,并研究了它们与治疗反应及患者生存率的关系。
本研究纳入了178例接受了肿瘤细胞减灭术并随后接受铂类化疗的上皮性卵巢癌患者;其中75例患者还接受了紫杉醇治疗。手术时采集的新鲜肿瘤样本,采用实时聚合酶链反应分析检测βIII-微管蛋白和Stathmin的信使核糖核酸表达。评估这些分子与治疗反应、疾病进展和总生存率的关系。
与低Stathmin表达相比,高Stathmin表达与更差的无疾病进展生存期和总生存期相关。这种关联独立于患者年龄、疾病分期、肿瘤分级、组织学类型和残余肿瘤大小,且在接受铂类加紫杉醇治疗的患者中观察到,但在仅接受铂类治疗而未接受紫杉醇治疗的患者中未观察到,这表明肿瘤组织中Stathmin的表达可能会干扰紫杉醇治疗。βIII-微管蛋白未观察到类似效应,尽管在仅接受铂类治疗而未接受紫杉醇治疗的患者中,高βIII-微管蛋白表达与疾病进展相关。治疗反应与微管蛋白或Stathmin表达之间未观察到关联。βIII-微管蛋白和Stathmin的表达水平显著相关。
高Stathmin表达预示着接受紫杉醇和铂类化疗的卵巢癌患者预后不良。这一发现支持了Stathmin可能干扰紫杉醇治疗,从而导致卵巢癌患者预后不良的可能性。