Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway ; Department of Gynecology and Obstetrics, Haukeland University Hospital, Bergen, Norway.
Centre for Cancer Biomarkers, Department of Clinical Science, The University of Bergen, Bergen, Norway.
PLoS One. 2014 Feb 25;9(2):e90141. doi: 10.1371/journal.pone.0090141. eCollection 2014.
Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.
Stathmin 是许多癌症（包括子宫内膜癌）的预后标志物。临床前研究主要在乳腺癌中表明，Stathmin 可能还是紫杉醇反应的预测标志物。我们首先评估了紫杉醇治疗前后子宫内膜癌细胞系对紫杉醇的反应，然后研究了转移性子宫内膜癌中紫杉醇化疗的临床反应与肿瘤中 Stathmin 蛋白水平的关系。还在转移性病变中确定了 Stathmin 水平，分析了疾病进展时生物标志物状态的变化。Stathmin 的敲低提高了对紫杉醇敏感的子宫内膜癌细胞系对紫杉醇的敏感性，而对紫杉醇敏感性较低的细胞系也有改善。在临床样本中，高 Stathmin 水平与紫杉醇化疗反应差和疾病特异性生存时间缩短相关，仅在接受此类联合治疗的患者中观察到。Stathmin 水平从原发性转移病变显著增加。这项研究表明，临床前和临床数据均支持 Stathmin 可能是子宫内膜癌对紫杉醇治疗反应的预测生物标志物。在开始治疗前重新评估转移性病变中的 Stathmin 水平可能是相关的。在随机临床试验中的验证也很重要。
