The Clinical Significance of Cancer Stem Cell Markers ALDH1A1 and CD133 in Lung Adenocarcinoma

被引：27

作者：

Miyata, Takeaki ^{[1
,2
]}

Oyama, Tsunehiro ^{[1
,3
]}

Yoshimatsu, Takashi ^{[2
]}

Higa, Hanae ^{[2
]}

Kawano, Daigo ^{[2
]}

Sekimura, Atsushi ^{[4
]}

Yamashita, Naoki ^{[5
]}

So, Tetsuya ^{[5
]}

Gotoh, Akinobu ^{[1
]}

机构：

[1] Hyogo Coll Med, Lab Cell & Gene Therapy, Nishinomiya, Hyogo, Japan

[2] Fukuoka Wajiro Hosp, Dept Thorac Surg, Fukuoka, Japan

[3] Imamitsu Home Care Clin, Kitakyushu, Japan

[4] Shin Takeo Hosp, Dept Thorac Surg, Takeo, Japan

[5] Shin Komonji Hosp, Dept Thorac Surg, Kitakyushu, Japan

来源：

ANTICANCER RESEARCH | 2017年 / 37卷 / 05期

关键词：

Lung adenocarcinoma; ALDH1A1; CD133; cancer stem cells; CSCs; ALDEHYDE DEHYDROGENASE 1A1; PROGNOSTIC-SIGNIFICANCE; EXPRESSION; RADIORESISTANCE; CLASSIFICATION; ASSOCIATION; POPULATION; TUMORS;

D O I：

10.21873/anticanres.11597

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: Aldehyde dehydrogenase-1A1 (ALDH1A1) and CD133 have been identified as markers of cancer stem cells (CSCs). We investigated the expression of these markers and their clinical significance in lung adenocarcinoma. Materials and Methods: An immunohistochemical analysis of ALDH1A1 and CD133 expression of 92 lung adenocarcinomas was performed. The association between the expression of both markers and cancer-related death and recurrence was determined. Results: Cancer-related death and tumor recurrence were observed in 15 and 17 cases, respectively. The expression of CD133, but not ALDHA1A, was significantly associated with poorer overall survival (p<0.0001) and shorter disease-free interval (DFI) (p<0.0001). Multivariate analysis revealed that double negativity was independently associated with increased survival (hazard ratio(HR)= 16.1, p=0.0004) and a longer DFI (HR=9.5,p=0.0007). Conclusion: We propose that as a functional marker, ALDH1A1 positivity may influence the viability of CSCs. The findings suggest that it is important to evaluate the expression of both markers.

引用

页码：2541 / 2547

页数：7

共 27 条

[1] The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer [J].

Alamgeer, Muhammad ;

Ganju, Vinod ;

Szczepny, Anette ;

Russell, Prudence A. ;

Prodanovic, Zdenka ;

Kumar, Beena ;

Wainer, Zoe ;

Brown, Tracey ;

Schneider-Kolsky, Michal ;

Conron, Matthew ;

Wright, Gavin ;

Watkins, D. Neil .

THORAX, 2013, 68 (12) :1095-1104

[2] Microenvironment-Modulated Metastatic CD133+/CXCR4+/EpCAM- Lung Cancer-Initiating Cells Sustain Tumor Dissemination and Correlate with Poor Prognosis [J].

Bertolini, Giulia ;

D'Amico, Lucia ;

Moro, Massimo ;

Landoni, Elena ;

Perego, Paola ;

Miceli, Rosalba ;

Gatti, Laura ;

Andriani, Francesca ;

Wong, Donald ;

Caserini, Roberto ;

Tortoreto, Monica ;

Milione, Massimo ;

Ferracini, Riccardo ;

Mariani, Luigi ;

Pastorino, Ugo ;

Roato, Ilaria ;

Sozzi, Gabriella ;

Roz, Luca .

CANCER RESEARCH, 2015, 75 (17) :3636-3649

[3] Association of reactive oxygen species levels and radioresistance in cancer stem cells [J].

Diehn, Maximilian ;

Cho, Robert W. ;

Lobo, Neethan A. ;

Kalisky, Tomer ;

Dorie, Mary Jo ;

Kulp, Angela N. ;

Qian, Dalong ;

Lam, Jessica S. ;

Ailles, Laurie E. ;

Wong, Manzhi ;

Joshua, Benzion ;

Kaplan, Michael J. ;

Wapnir, Irene ;

Dirbas, Frederick M. ;

Somlo, George ;

Garberoglio, Carlos ;

Paz, Benjamin ;

Shen, Jeannie ;

Lau, Sean K. ;

Quake, Stephen R. ;

Brown, J. Martin ;

Weissman, Irving L. ;

Clarke, Michael F. .

NATURE, 2009, 458 (7239) :780-U123

[4] Identification and expansion of the tumorigenic lung cancer stem cell population [J].

Eramo, A. ;

Lotti, F. ;

Sette, G. ;

Pilozzi, E. ;

Biffoni, M. ;

Di Virgilio, A. ;

Conticello, C. ;

Ruco, L. ;

Peschle, C. ;

De Maria, R. .

CELL DEATH AND DIFFERENTIATION, 2008, 15 (03) :504-514

[5] The role of LGR5 and ALDH1A1 in non-small cell lung cancer: Cancer progression and prognosis [J].

Gao, Fei ;

Zhou, Bin ;

Xu, Jun-Chi ;

Gao, Xin ;

Li, Shu-Xiang ;

Zhu, Geng-Chao ;

Zhang, Xue Guang ;

Yang, Chen .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2015, 462 (02) :91-98

[6] The IASLC lung cancer staging project: Proposals for the revision of he TNM stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours [J].

Goldstraw, Peter ;

Crowley, John ;

Chansky, Kari ;

Giroux, Dorothy J. ;

Groome, Patti A. ;

Rami-Porta, Ramon ;

Postmus, Pieter E. ;

Rusch, Valerie ;

Sobin, Leslie .

JOURNAL OF THORACIC ONCOLOGY, 2007, 2 (08) :706-714

[7] Side population in human lung cancer cell lines and tumors is enriched with stem-like cancer cells [J].

Ho, Maria M. ;

Ng, Alvin V. ;

Lam, Stephen ;

Hung, Jaclyn Y. .

CANCER RESEARCH, 2007, 67 (10) :4827-4833

[8] Aldehyde Dehydrogenase 1 Is a Tumor Stem Cell-Associated Marker in Lung Cancer [J].

Jiang, Feng ;

Qiu, Qi ;

Khanna, Abha ;

Todd, Nevins W. ;

Deepak, Janaki ;

Xing, Lingxiao ;

Wang, Huijun ;

Liu, Zhenqiu ;

Su, Yun ;

Stass, Sanford A. ;

Katz, Ruth L. .

MOLECULAR CANCER RESEARCH, 2009, 7 (03) :330-338

[9] Old disease, new culprit: Tumor stem cells in cancer [J].

Lee, John T. ;

Herlyn, Meenhard .

JOURNAL OF CELLULAR PHYSIOLOGY, 2007, 213 (03) :603-609

[10] Aldehyde Dehydrogenase 1A1 Possesses Stem-Like Properties and Predicts Lung Cancer Patient Outcome [J].

Li, Xiao ;

Wan, Liyan ;

Geng, Jian ;

Wu, Chin-Lee ;

Bai, Xiaoyan .

JOURNAL OF THORACIC ONCOLOGY, 2012, 7 (08) :1235-1245

← 1 2 3 →