title: Clinical relevance of EMT and stem-like gene expression in circulating tumor cells of metastatic colorectal cancer patients.
abstract: Using approved methods, circulating tumor cells (CTCs) are only isolated from blood in 30%-50% of metastatic colorectal cancer (mCRC) patients. We previously validated a technique to isolate circulating tumor cells (CTCs) in a cohort of mCRC patients by combining immunomagnetic enrichment of EpCAM+/CD45-cells with qRT-PCR amplification of CK20 and survivin expression. Here, we examined the prognostic utility of CTC epithelial-mesenchymal transition (EMT) and stem cell gene expression. An 8 ml blood sample was collected from 78 consecutive mCRC patients before treatment with investigational and standard chemotherapeutics. The mRNA expression of EMT (PI3Kα, Akt-2, Twist1) and stem cell (ALDH1) markers was measured. Associations between CTC gene expression and progression-free survival (PFS) and overall survival (OS) were determined using Cox regression models. Among patients without CK20 or survivin-expressing CTCs (n=17), 55% had expression of ALDH1, PI3Kα and/or Akt-2. Patients with positive CTC Akt-2 expression had a significantly shorter median PFS (3.0 versus 4.0 months) compared with those without CTC Akt-2 expression in univariable (hazard ratio (HR)=1.61; log-rank P=0.034) and multivariable analyses (HR=1.70; adjusted P=0.041). In univariable analysis, CTC ALDH1 expression was associated with shorter OS (10.0 versus 38.6 months; HR=2.04, P=0.021). Patients with CTCs expressing ALDH1, PI3Kα and/or Akt-2 had a significantly inferior PFS (3.0 versus 7.7 months; HR=1.88, P=0.015) and OS (10.0 versus 26.8+ months; HR=2.25, P=0.050) in univariable, but not multivariable, analysis.
  
  
  
  CTC Akt-2 expression may serve as a clinically useful prognostic marker in mCRC patients and warrants further evaluation in prospective trials.
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Y
authors: Y
authors: Ning
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: W
authors: W
authors: Zhang
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: D L
authors: DL
authors: Hanna
authors: Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: D
authors: D
authors: Yang
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: S
authors: S
authors: Okazaki
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: M D
authors: MD
authors: Berger
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: Y
authors: Y
authors: Miyamoto
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: M
authors: M
authors: Suenaga
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: M
authors: M
authors: Schirripa
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: A
authors: A
authors: El-Khoueiry
authors: Division of Medical Oncology, Sharon A. Carpenter Laboratory, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.|Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors: H-J
authors: HJ
authors: Lenz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D011379:Prognosis; D000077982:Progression-Free Survival
chemical_list: D014408:Biomarkers, Tumor