Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers

Autor: Stephen J. Kron, O. Fayanju, O. Balogun, M.A. Beckett, Ralph R. Weichselbaum, Nikolai N. Khodarev, Christian A. Fernandez, G. Qiao, Robert K. Chin, Jukes P. Namm, Mitchell C. Posner, Kinga B. Skowron, Xiaona Huang, Wenxin Zheng, Sean P. Pitroda, Gary D. Steinberg, M. L. Zenner
Rok vydání: 2016
Předmět:
0301 basic medicine
Oncology
Male
Cellular differentiation
Mice
SCID
Transcriptome
Mice
Basal (phylogenetics)
0302 clinical medicine
2.1 Biological and endogenous factors
Prospective Studies
Aetiology
Stage (cooking)
Cancer
Tumor
Multidisciplinary
medicine.diagnostic_test
biology
Cell Differentiation
Middle Aged
Flow Cytometry
Prognosis
3. Good health
Gene Expression Regulation
Neoplastic
030220 oncology & carcinogenesis
Female
Urologic Diseases
medicine.medical_specialty
SCID
Article
Flow cytometry
03 medical and health sciences
Clinical Research
Internal medicine
medicine
Biomarkers
Tumor
Animals
Humans
cdc25 Phosphatases
CD90
Aged
Neoplastic
Bladder cancer
CD44
medicine.disease
Xenograft Model Antitumor Assays
030104 developmental biology
Gene Expression Regulation
Urinary Bladder Neoplasms
biology.protein
Biomarkers
Zdroj: Scientific Reports
Scientific reports, vol 6, iss 1
ISSN: 2045-2322
Popis: Strategies to identify tumors at highest risk for treatment failure are currently under investigation for patients with bladder cancer. We demonstrate that flow cytometric detection of poorly differentiated basal tumor cells (BTCs), as defined by the co-expression of CD90, CD44 and CD49f, directly from patients with early stage tumors (T1-T2 and N0) and patient-derived xenograft (PDX) engraftment in locally advanced tumors (T3-T4 or N+) predict poor prognosis in patients with bladder cancer. Comparative transcriptomic analysis of bladder tumor cells isolated from PDXs indicates unique patterns of gene expression during bladder tumor cell differentiation. We found cell division cycle 25C (CDC25C) overexpression in poorly differentiated BTCs and determined that CDC25C expression predicts adverse survival independent of standard clinical and pathologic features in bladder cancer patients. Taken together, our findings support the utility of BTCs and bladder cancer PDX models in the discovery of novel molecular targets and predictive biomarkers for personalizing oncology care for patients.
Databáze: OpenAIRE
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