title: Genomic analysis identifies unique signatures predictive of brain, lung, and liver relapse.
abstract: The ability to predict metastatic potential could be of great clinical importance, however, it is uncertain if predicting metastasis to specific vital organs is feasible. As a first step in evaluating metastatic predictions, we analyzed multiple primary tumors and metastasis pairs and determined that >90% of 298 gene expression signatures were found to be similarly expressed between matched pairs of tumors and metastases; therefore, primary tumors may be a good predictor of metastatic propensity. Next, using a dataset of >1,000 human breast tumor gene expression microarrays we determined that HER2-enriched subtype tumors aggressively spread to the liver, while basal-like and claudin-low subtypes colonize the brain and lung. Correspondingly, brain and lung metastasis signatures, along with embryonic stem cell, tumor initiating cell, and hypoxia signatures, were also strongly expressed in the basal-like and claudin-low tumors. Interestingly, low "Differentiation Scores," or high expression of the aforementioned signatures, further predicted for brain and lung metastases. In total, these data identify that depending upon the organ of relapse, a combination of gene expression signatures most accurately predicts metastatic behavior.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, 450 West Drive, CB7295, Chapel Hill, NC 27599, USA.
authors.forename: J Chuck
authors.initials: JC
authors.lastname: Harrell
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.forename: Cheng
authors.initials: C
authors.lastname: Fan
authors.forename: Xiaping
authors.initials: X
authors.lastname: He
authors.forename: Lisa
authors.initials: L
authors.lastname: Carey
authors.forename: Carey
authors.initials: C
authors.lastname: Anders
authors.forename: Matthew
authors.initials: M
authors.lastname: Ewend
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D016000:Cluster Analysis; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000556:secondary*; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors