Accumulation of ALDH1-positive cells after neoadjuvant chemotherapy predicts treatment resistance and prognosticates poor outcome in ovarian cancer

被引:47
作者
Ayub, Tiyasha H. [1 ]
Keyver-Paik, Mignon-Denise [1 ]
Debald, Manuel [1 ]
Rostamzadeh, Babak [2 ]
Thiesler, Thore [2 ]
Schroeder, Lars [1 ]
Barchet, Winfried [3 ]
Abramian, Alina [1 ]
Kaiser, Christina [1 ]
Kristiansen, Glen [2 ]
Kuhn, Walther [1 ]
Kuebler, Kirsten [1 ]
机构
[1] Univ Bonn, Dept Obstet & Gynecol, Ctr Integrated Oncol, Bonn, Germany
[2] Ctr Integrated Oncol, Inst Pathol, Bonn, Germany
[3] Ctr Integrated Oncol, Inst Clin Chem & Clin Pharmacol, Bonn, Germany
关键词
ovarian cancer; predictive marker; prognostic marker; ALDH1; cancer stem-like cell; STEM-CELLS; ALDEHYDE DEHYDROGENASE; EXPRESSION; MARKER; CONTRIBUTE; CISPLATIN; SURGERY; PATIENT; ALDH1; LINES;
D O I
10.18632/oncotarget.4103
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Although ovarian cancer is a highly chemosensitive disease, it is only infrequently cured. One of the major reasons lies in the presence of drug-resistant cancer stem-like cells, sufficient to fuel recurrence. We phenotyped cancer stem-like cells by flow cytometry and immunohistochemistry in 55 matched samples before and after taxane/platinum-based neoadjuvant chemotherapy. All used markers of stemness (ALDH1, CD24, CD117, CD133) isolated low frequencies of malignant cells. ALDH1 was the most valuable marker for tracking stemness in vivo. The enrichment of ALDH1 expression after treatment was associated with a poor response to chemotherapy, with platinum resistance and independently prognosticated unfavorable outcome. Our results suggest that increased ALDH1 expression after treatment identifies patients with aggressive tumor phenotypes.
引用
收藏
页码:16437 / 16448
页数:12
相关论文
共 55 条
[1]   Short-term single treatment of chemotherapy results in the enrichment of ovarian cancer stem cell-like cells leading to an increased tumor burden [J].
Abubaker, Khalid ;
Latifi, Ardian ;
Luwor, Rod ;
Nazaretian, Simon ;
Zhu, Hongjian ;
Quinn, Michael A. ;
Thompson, Erik W. ;
Findlay, Jock K. ;
Ahmed, Nuzhat .
MOLECULAR CANCER, 2013, 12
[2]   Changes in aldehyde dehydrogenase-1 expression during neoadjuvant chemotherapy predict outcome in locally advanced breast cancer [J].
Alamgeer, Muhammad ;
Ganju, Vinod ;
Kumar, Beena ;
Fox, Jane ;
Hart, Stewart ;
White, Michelle ;
Harris, Marion ;
Stuckey, John ;
Prodanovic, Zdenka ;
Schneider-Kolsky, Michal Elisabeth ;
Watkins, D. Neil .
BREAST CANCER RESEARCH, 2014, 16 (02)
[3]  
[Anonymous], MOL CANC
[4]   Prediction of response to neoadjuvant chemotherapy by sequential F-18-fluorodeoxyglucose positron emission tomography in patients with advanced-stage ovarian cancer [J].
Avril, N ;
Sassen, S ;
Schmalfeldt, B ;
Naehrig, J ;
Rutke, S ;
Weber, WA ;
Werner, M ;
Graeff, H ;
Schwaiger, M ;
Kuhn, W .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (30) :7445-7453
[5]   Epigenetic regulation of CD133 and tumorigenicity of CD133+ovarian cancer cells [J].
Baba, T. ;
Convery, P. A. ;
Matsumura, N. ;
Whitaker, R. S. ;
Kondoh, E. ;
Perry, T. ;
Huang, Z. ;
Bentley, R. C. ;
Mori, S. ;
Fujii, S. ;
Marks, J. R. ;
Berchuck, A. ;
Murphy, S. K. .
ONCOGENE, 2009, 28 (02) :209-218
[6]   Stem and progenitor-like cells contribute to the aggressive behavior of human epithelial ovarian cancer [J].
Bapat, SA ;
Mali, AM ;
Koppikar, CB ;
Kurrey, NK .
CANCER RESEARCH, 2005, 65 (08) :3025-3029
[7]   Cancer stem cell and cancer stemloids [J].
Blagosklonny, Mikhail V. .
CANCER BIOLOGY & THERAPY, 2007, 6 (11) :1684-1690
[8]   Why therapeutic response may not prolong the life of a cancer patient - Selection for oncogenic resistance [J].
Blagosklonny, MV .
CELL CYCLE, 2005, 4 (12) :1693-1698
[9]   ALDH1 expression correlates with favorable prognosis in ovarian cancers [J].
Chang, Bin ;
Liu, Guangzhi ;
Xue, Fengxia ;
Rosen, Daniel G. ;
Xiao, Lianchun ;
Wang, Xuemei ;
Liu, Jinsong .
MODERN PATHOLOGY, 2009, 22 (06) :817-823
[10]   CD133 Expression and the Prognosis of Colorectal Cancer: A Systematic Review and Meta-Analysis [J].
Chen, Shicai ;
Song, Xinming ;
Chen, Zhihui ;
Li, Xinxin ;
Li, Mingzhe ;
Liu, Haiying ;
Li, Jianchang .
PLOS ONE, 2013, 8 (02)