Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas

Timothy Henderson, Mingyi Chen, Morgan A. Darrow, Chin Shang Li, Chi Lu Chiu, Arta M. Monjazeb, William J. Murphy, Robert J. Canter

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. Methods We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan–Meier analysis. Results Of the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. Conclusions Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

Original languageEnglish (US)
Pages (from-to)207-214
Number of pages8
JournalJournal of Surgical Research
Volume223
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

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Neoplastic Stem Cells
Sarcoma
Epidermal Growth Factor Receptor
Aldehyde Dehydrogenase
Atlases
Genome
Neoplasms
Survival
Multivariate Analysis
Extremities
Biomarkers
Databases
Confidence Intervals
Neoplasm Metastasis
Recurrence
Drug Therapy

Keywords

  • ALDH
  • Cancer stem cells
  • CD44
  • EGFR
  • Oncologic outcomes
  • Soft-tissue sarcoma

ASJC Scopus subject areas

  • Surgery

Cite this

Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas. / Henderson, Timothy; Chen, Mingyi; Darrow, Morgan A.; Li, Chin Shang; Chiu, Chi Lu; Monjazeb, Arta M.; Murphy, William J.; Canter, Robert J.

In: Journal of Surgical Research, Vol. 223, 01.03.2018, p. 207-214.

Research output: Contribution to journalArticle

Henderson, Timothy ; Chen, Mingyi ; Darrow, Morgan A. ; Li, Chin Shang ; Chiu, Chi Lu ; Monjazeb, Arta M. ; Murphy, William J. ; Canter, Robert J. / Alterations in cancer stem-cell marker CD44 expression predict oncologic outcome in soft-tissue sarcomas. In: Journal of Surgical Research. 2018 ; Vol. 223. pp. 207-214.
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abstract = "Background Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. Methods We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan–Meier analysis. Results Of the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39{\%}) experienced distant recurrence, and four (17{\%}) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95{\%} confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. Conclusions Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.",
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AU - Henderson, Timothy

AU - Chen, Mingyi

AU - Darrow, Morgan A.

AU - Li, Chin Shang

AU - Chiu, Chi Lu

AU - Monjazeb, Arta M.

AU - Murphy, William J.

AU - Canter, Robert J.

PY - 2018/3/1

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N2 - Background Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. Methods We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan–Meier analysis. Results Of the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. Conclusions Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

AB - Background Cancer stem cells (CSCs) have been shown to resist chemotherapy and promote metastasis after cytotoxic therapies. We sought to determine if the expression of CSC markers (aldehyde dehydrogenase [ALDH], CD44, and epidermal growth factor receptor [EGFR]) predicted outcomes in soft-tissue sarcoma (STS) patients. Methods We queried an institutional database of 23 STS patients and evaluated immunohistochemical expression of CSC markers ALDH, CD44, and EGFR. The Cancer Genome Atlas (TCGA) was also queried for STS clinical and genomic data. Disease-specific (DSS) and overall survival (OS) were assessed by univariate and Kaplan–Meier analysis. Results Of the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27 months, nine patients (39%) experienced distant recurrence, and four (17%) died of disease. Mean H-scores at diagnosis (±standard error of the mean) for CD44, ALDH1, and EGFR were 169 ± 27, 77 ± 15, and 144 ± 23, respectively. On univariate analysis, there was a trend for increased CD44 score to predict both worse DSS and OS (hazard ratio = 1.01, 95% confidence interval 1-1.02, P = 0.056), whereas ALDH and EGFR scores did not. Analysis of 74 TCGA STS cases with complete clinical and genomic data revealed that CD44 copy number alterations predicted worse DSS (9.89 months versus 72.5 months, P = 0.007) and a trend for worse OS (14.03 months versus 38.6 months, P = 0.12), whereas ALDH1 and EGFR copy number alteration did not. Multivariate analysis of the combined data sets was consistent with worse DSS among patients with higher CD44 expression. Conclusions Institutional and national TCGA data show the association of elevated baseline CD44 expression with worse STS outcomes. Further study of CD44 as a possible novel STS biomarker appears indicated.

KW - ALDH

KW - Cancer stem cells

KW - CD44

KW - EGFR

KW - Oncologic outcomes

KW - Soft-tissue sarcoma

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