title: IGFBP1 in epithelial circulating tumor cells as a potential response marker to selective internal radiation therapy in hepatocellular carcinoma.
abstract: BACKGROUND
  Local ablative techniques such as selective internal radiation therapy (SIRT) have become the mainstay of treating hepatocellular carcinoma (HCC) in the bridging-to-transplant and palliative setting. We recently demonstrated that epithelial circulating tumor cells (CTCs) correlate to an unfavorable outcome. We wanted to scrutinize whether molecular markers detected in this specific CTC subgroup may also have clinical implications.
  
  
  METHODS
  Mononuclear cells and CTCs were isolated from peripheral blood samples using density gradient centrifugation followed by depletion of hematopoietic and enrichment of epithelial (EpCAM(+)) cells employing immunomagnetic beads. The mRNA expression of candidate markers was correlated with response to SIRT in 25 patients using quantitative real-time reverse-transcription PCR.
  
  
  RESULTS
  IGFBP1 mRNA expression levels were significantly correlated with time to progression in a Kaplan-Meier log rank test (p = 0.04; 0 vs 4 months) and receiver operating characteristic analysis demonstrated a potential use to predict patients with shortened time to progression (area under the curve: 0.8; 95% CI: 0.44-0.98; p = 0.03).
  
  
  CONCLUSIONS
  The EpCAM fraction of CTCs may be useful to detect novel molecular markers to individualize treatment decision in patients with HCC.
authors.affiliation: Department of Medical Oncology, Molecular Oncology Risk-Profile Evaluation, West German Cancer Center, University Hospital of Essen, Essen, Germany.
authors.forename: Ivonne
authors.initials: I
authors.lastname: Nel
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.forename: Frank
authors.initials: F
authors.lastname: Weber
authors.forename: Barbara
authors.initials: B
authors.lastname: Sitek
authors.forename: Martin
authors.initials: M
authors.lastname: Eisenacher
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Meyer
authors.forename: Joerg F
authors.initials: JF
authors.lastname: Schlaak
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D018450:Disease Progression; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000378:metabolism* / Q000528:radiation effects; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood* / Q000235:genetics; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000378:metabolism* / Q000528:radiation effects; D059467:Transcriptome / Q000528:radiation effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D018970:Insulin-Like Growth Factor Binding Protein 1
keywords: AFP; EpCAM; IGFBP1; SIRT; circulating tumor cells; epithelial cells; hepatocellular carcinoma; peripheral blood