title: Basal Tumor Cell Isolation and Patient-Derived Xenograft Engraftment Identify High-Risk Clinical Bladder Cancers.
abstract: 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.
authors: University of Chicago Medicine, Dept. of Surgery, Chicago, IL, USA.
authors: K B
authors: KB
authors: Skowron
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: S P
authors: SP
authors: Pitroda
authors: University of Chicago Medicine, Dept. of Surgery, Chicago, IL, USA.|Loma Linda University Health, Dept. of Surgery, Loma Linda, CA USA.
authors: J P
authors: JP
authors: Namm
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: O
authors: O
authors: Balogun
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: M A
authors: MA
authors: Beckett
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.|University of Illinois at Chicago, Chicago, IL USA.
authors: M L
authors: ML
authors: Zenner
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.
authors: O
authors: O
authors: Fayanju
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: X
authors: X
authors: Huang
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.|University of Illinois at Chicago, Chicago, IL USA.
authors: C
authors: C
authors: Fernandez
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: W
authors: W
authors: Zheng
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: G
authors: G
authors: Qiao
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.|University of California Los Angeles, Dept. of Radiation Oncology, Los Angeles, CA, USA.
authors: R
authors: R
authors: Chin
authors: University of Chicago, Dept. of Molecular Genetics and Cell Biology, Chicago, IL, USA.
authors: S J
authors: SJ
authors: Kron
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: N N
authors: NN
authors: Khodarev
authors: University of Chicago Medicine, Dept. of Surgery, Chicago, IL, USA.
authors: M C
authors: MC
authors: Posner
authors: University of Chicago Medicine, Dept. of Surgery, Chicago, IL, USA.
authors: G D
authors: GD
authors: Steinberg
authors: University of Chicago Medicine, Dept. of Radiation and Cellular Oncology, Chicago, IL, USA.|The Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL, USA.
authors: R R
authors: RR
authors: Weichselbaum
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D016513:Mice, SCID; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D020687:cdc25 Phosphatases / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases