title: Gene Signature Associated with Upregulation of the Wnt/β-Catenin Signaling Pathway Predicts Tumor Response to Transarterial Embolization.
abstract: OBJECTIVE
  To identify gene mutations in tumors undergoing transarterial embolization and explore the relationship between gene mutations and tumor response to embolization.
  
  
  METHODS
  This was a retrospective review that included 17 patients with primary or metastatic liver tumors treated with embolization and had specimens analyzed for a 341-gene panel next-generation sequence assay. Pathologic conditions included hepatocellular, carcinoid, pancreatic neuroendocrine, melanoma, medullary thyroid, and liver acinar-cell carcinoma. Disease, procedure data, and tumor response data were collected. Dimensionality reduction was performed by using principal component analysis. A linear support vector machine was used to learn a prediction rule and identify the genes most predictive of objective tumor response (partial or complete) per modified Response Evaluation Criteria In Solid Tumors. Cross-validation was used to test the prediction on the holdout set. Permutation testing was used to determine statistical significance of prediction accuracy. Recursive feature elimination was used to identify the most predictive genes.
  
  
  RESULTS
  At 4 months after embolization, 9 tumors showed a response and 8 did not. Using the top two principal components, prediction accuracy of the gene mutation signature was 70% (±11%), which was statistically significant (P < .05). The most predictive genes were CTNNB1, MEN1, and NCOR1: three genes associated with the Wnt/β-catenin and hypoxia signaling pathways.
  
  
  CONCLUSIONS
  This study identifies gene mutations in tumors treated with transarterial embolization. A gene-mutation signature obtained from the mutation data suggests that upregulation of the Wnt/β-catenin signaling pathway may be associated with sensitivity to embolization.
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065. Electronic address: etay.ziv@gmail.com.
authors.forename: Etay
authors.initials: E
authors.lastname: Ziv
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Hooman
authors.initials: H
authors.lastname: Yarmohammadi
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: F Edward
authors.initials: FE
authors.lastname: Boas
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Elena Nadia
authors.initials: EN
authors.lastname: Petre
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Karen T
authors.initials: KT
authors.lastname: Brown
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Solomon
authors.affiliation: Human Oncology and Pathogenesis Program, Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: David
authors.initials: D
authors.lastname: Solit
authors.affiliation: Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Diane
authors.initials: D
authors.lastname: Reidy
authors.affiliation: Interventional Radiology Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, Howard-118, 1275 York Ave., New York, NY10065.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Erinjeri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016014:Linear Models; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D056971:Nuclear Receptor Co-Repressor 1 / Q000235:genetics; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D015203:Reproducibility of Results; D012189:Retrospective Studies; D060388:Support Vector Machine; D013997:Time Factors; D059467:Transcriptome; D016896:Treatment Outcome; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C105373:MEN1 protein, human; C539127:NCOR1 protein, human; D056971:Nuclear Receptor Co-Repressor 1; D011518:Proto-Oncogene Proteins; D051176:beta Catenin