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

Autor: Morgan A. Darrow, Mingyi Chen, Arta M. Monjazeb, Chin-Shang Li, Robert J. Canter, Timothy Henderson, Chi Lu Chiu, William J. Murphy
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Oncology
medicine.medical_treatment
Oncologic outcomes
Metastasis
0302 clinical medicine
Stem Cell Research - Nonembryonic - Human
80 and over
CD44
Cancer
Aged
80 and over
Univariate analysis
biology
Cancer stem cells
Soft tissue sarcoma
Sarcoma
Middle Aged
Immunohistochemistry
Isoenzymes
ErbB Receptors
Hyaluronan Receptors
030220 oncology & carcinogenesis
Neoplastic Stem Cells
Soft-tissue sarcoma
Female
Adult
medicine.medical_specialty
EGFR
Clinical Sciences
ALDH
Article
Aldehyde Dehydrogenase 1 Family
03 medical and health sciences
Clinical Research
Cancer stem cell
Internal medicine
Genetics
medicine
Humans
Aged
Chemotherapy
business.industry
Human Genome
Retinal Dehydrogenase
Stem Cell Research
medicine.disease
030104 developmental biology
biology.protein
Surgery
business
Zdroj: Journal of Surgical Research. 223:207-214
ISSN: 0022-4804
Popis: BackgroundCancer 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.MethodsWe 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.ResultsOf the 23 institutional patients, the majority was female, had high-grade tumors and had extremity tumors. With a median follow-up of 27months, 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 (9.89months versus 72.5months, P=0.007) and a trend for worse OS (14.03months versus 38.6months, 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.ConclusionsInstitutional 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.
Databáze: OpenAIRE
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