Stathmin Protein Level, a Potential Predictive Marker for Taxane Treatment Response in Endometrial Cancer

被引:34
|
作者
Werner, Henrica M. J. [1 ,2 ]
Trovik, Jone [1 ,2 ]
Halle, Mari K. [1 ]
Wik, Elisabeth [1 ,4 ]
Akslen, Lars A. [3 ,4 ]
Birkeland, Even [1 ]
Bredholt, Therese [1 ]
Tangen, Ingvild L. [1 ,2 ]
Krakstad, Camilla [1 ]
Salvesen, Helga B. [1 ,2 ]
机构
[1] Univ Bergen, Dept Clin Sci, Ctr Canc Biomarkers, Bergen, Norway
[2] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway
[3] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, Bergen, Norway
[4] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway
来源
PLOS ONE | 2014年 / 9卷 / 02期
关键词
TISSUE CONFIRMATION; CELL-DEATH; EXPRESSION; CARCINOMA; OVEREXPRESSION; SENSITIVITY; PACLITAXEL; THERAPY; GENE; PHOSPHORYLATION;
D O I
10.1371/journal.pone.0090141
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:9
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