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

Muhammad Alamgeer, Vinod Ganju, Anette Szczepny, Prudence A Russell, Zdenka Prodanovic, Beena Kumar, Zoe Wainer, Tracey Jean Brown, Michal Schneider-Kolsky, Matthew Conron, Gavin Wright, David Neil Watkins

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Abstract

Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7 and 50.7 of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.
Original languageEnglish
Pages (from-to)1095 - 1104
Number of pages10
JournalThorax
Volume68
Issue number12
DOIs
Publication statusPublished - 2013

Cite this

Alamgeer, Muhammad ; Ganju, Vinod ; Szczepny, Anette ; Russell, Prudence A ; Prodanovic, Zdenka ; Kumar, Beena ; Wainer, Zoe ; Brown, Tracey Jean ; Schneider-Kolsky, Michal ; Conron, Matthew ; Wright, Gavin ; Watkins, David Neil. / The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. In: Thorax. 2013 ; Vol. 68, No. 12. pp. 1095 - 1104.
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title = "The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer",
abstract = "Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7 and 50.7 of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.",
author = "Muhammad Alamgeer and Vinod Ganju and Anette Szczepny and Russell, {Prudence A} and Zdenka Prodanovic and Beena Kumar and Zoe Wainer and Brown, {Tracey Jean} and Michal Schneider-Kolsky and Matthew Conron and Gavin Wright and Watkins, {David Neil}",
year = "2013",
doi = "10.1136/thoraxjnl-2012-203021",
language = "English",
volume = "68",
pages = "1095 -- 1104",
journal = "Thorax",
issn = "0040-6376",
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The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer. / Alamgeer, Muhammad; Ganju, Vinod; Szczepny, Anette; Russell, Prudence A; Prodanovic, Zdenka; Kumar, Beena; Wainer, Zoe; Brown, Tracey Jean; Schneider-Kolsky, Michal; Conron, Matthew; Wright, Gavin; Watkins, David Neil.

In: Thorax, Vol. 68, No. 12, 2013, p. 1095 - 1104.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The prognostic significance of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 expression in early stage non-small cell lung cancer

AU - Alamgeer, Muhammad

AU - Ganju, Vinod

AU - Szczepny, Anette

AU - Russell, Prudence A

AU - Prodanovic, Zdenka

AU - Kumar, Beena

AU - Wainer, Zoe

AU - Brown, Tracey Jean

AU - Schneider-Kolsky, Michal

AU - Conron, Matthew

AU - Wright, Gavin

AU - Watkins, David Neil

PY - 2013

Y1 - 2013

N2 - Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7 and 50.7 of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

AB - Expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and CD133 has been functionally associated with a stem cell phenotype in normal and malignant cells. The prevalence of such cells in solid tumours should therefore correlate with recurrence and/or metastasis following definitive surgical resection. The aim of this study was to evaluate the prognostic significance of ALDH1A1 and CD133 in surgically resected, early stage non-small cell lung cancer (NSCLC). METHODS: A retrospective analysis of ALDH1A1 and CD133 expression in 205 patients with pathologic stage I NSCLC was performed using immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: We identified 62 relapses and 58 cancer-related deaths in 144 stage 1A and 61 stage 1B patients, analysed at a median of 5-years follow-up. Overexpression of ALDH1A1 and CD133, detected in 68.7 and 50.7 of primary tumours, respectively, was an independent prognostic indicator for overall survival by multivariable Cox proportional hazard model (p=0.017 and 0.039, respectively). Overexpression of ALDH1A1, but not of CD133, predicted poor recurrence-free survival (p=0.025). When categorised into three groups according to expression of ALDH1A1/CD133, patients with overexpression of both ALDH1A1 and CD133 belonged to the group with the shortest recurrence-free and overall survival (p=0.015 and 0.017, respectively). CONCLUSIONS: Expression of ALDH1A1 and CD133, and coexpression of ALDH1A1 and CD133, is strongly associated with poor survival in early-stage NSCLC following surgical resection. These data are consistent with the hypothesis that expression of stem cell markers correlates with recurrence as an indirect measure of self-renewal capacity.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841805/pdf/thoraxjnl-2012-203021.pdf

U2 - 10.1136/thoraxjnl-2012-203021

DO - 10.1136/thoraxjnl-2012-203021

M3 - Article

VL - 68

SP - 1095

EP - 1104

JO - Thorax

JF - Thorax

SN - 0040-6376

IS - 12

ER -