Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

Kazuhiko Shien; Shinichi Toyooka; Kouichi Ichimura; Junichi Soh; Masashi Furukawa; Yuho Maki; Takayuki Muraoka; Norimitsu Tanaka; Tsuyoshi Ueno; Hiroaki Asano; Kazunori Tsukuda; Masaomi Yamane; Takahiro Oto; Katsuyuki Kiura; Shinichiro Miyoshi

doi:10.1016/j.lungcan.2012.02.006

Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

Kazuhiko Shien, Shinichi Toyooka, Kouichi Ichimura, Junichi Soh, Masashi Furukawa, Yuho Maki, Takayuki Muraoka, Norimitsu Tanaka, Tsuyoshi Ueno, Hiroaki Asano, Kazunori Tsukuda, Masaomi Yamane, Takahiro Oto, Katsuyuki Kiura, Shinichiro Miyoshi

Translational Molecular Pathology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72. months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P= 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P= 0.047) and cN2-3 single station metastasis (P= 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.

Original language	English (US)
Pages (from-to)	162-167
Number of pages	6
Journal	Lung Cancer
Volume	77
Issue number	1
DOIs	https://doi.org/10.1016/j.lungcan.2012.02.006
State	Published - Jul 2012

Keywords

ALDH1
CD133
Cancer stem cell
Chemoradiotherapy
Induction therapy
NSCLC

ASJC Scopus subject areas

Oncology
Pulmonary and Respiratory Medicine
Cancer Research

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10.1016/j.lungcan.2012.02.006

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Shien, K., Toyooka, S., Ichimura, K., Soh, J., Furukawa, M., Maki, Y., Muraoka, T., Tanaka, N., Ueno, T., Asano, H., Tsukuda, K., Yamane, M., Oto, T., Kiura, K., & Miyoshi, S. (2012). Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy. Lung Cancer, 77(1), 162-167. https://doi.org/10.1016/j.lungcan.2012.02.006

Shien, K, Toyooka, S, Ichimura, K, Soh, J, Furukawa, M, Maki, Y, Muraoka, T, Tanaka, N, Ueno, T, Asano, H, Tsukuda, K, Yamane, M, Oto, T, Kiura, K & Miyoshi, S 2012, 'Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy', Lung Cancer, vol. 77, no. 1, pp. 162-167. https://doi.org/10.1016/j.lungcan.2012.02.006

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abstract = "The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72. months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P= 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P= 0.047) and cN2-3 single station metastasis (P= 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.",

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author = "Kazuhiko Shien and Shinichi Toyooka and Kouichi Ichimura and Junichi Soh and Masashi Furukawa and Yuho Maki and Takayuki Muraoka and Norimitsu Tanaka and Tsuyoshi Ueno and Hiroaki Asano and Kazunori Tsukuda and Masaomi Yamane and Takahiro Oto and Katsuyuki Kiura and Shinichiro Miyoshi",

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AU - Shien, Kazuhiko

AU - Toyooka, Shinichi

AU - Ichimura, Kouichi

AU - Soh, Junichi

AU - Furukawa, Masashi

AU - Maki, Yuho

AU - Muraoka, Takayuki

AU - Tanaka, Norimitsu

AU - Ueno, Tsuyoshi

AU - Asano, Hiroaki

AU - Tsukuda, Kazunori

AU - Yamane, Masaomi

AU - Oto, Takahiro

AU - Kiura, Katsuyuki

AU - Miyoshi, Shinichiro

PY - 2012/7

Y1 - 2012/7

N2 - The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72. months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P= 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P= 0.047) and cN2-3 single station metastasis (P= 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.

AB - The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72. months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P= 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P= 0.047) and cN2-3 single station metastasis (P= 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.

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KW - Induction therapy

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Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy

Abstract

Keywords

ASJC Scopus subject areas

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