Original ResearchBasic and Translational—BiliaryGenomic and Genetic Characterization of Cholangiocarcinoma Identifies Therapeutic Targets for Tyrosine Kinase Inhibitors
Section snippets
Materials and Methods
Detailed information is provided in Supplementary Materials and Methods.
Transcriptomic Profiling Identifies 2 Distinct CCA Subclasses With Different Clinical Outcomes
The molecular profiles of the resected tumors were readily distinguishable from a group of matched noncancerous surrounding livers (Supplementary Figure 1A). This classification was confirmed by Bayesian compound covariate prediction modeling with 97% accuracy (95% confidence interval [CI], 0.93−0.99; P < .0001) (Supplementary Figure 1B). Within the cohort, the resected tumors of hilar (36/104) and peripheral type (68/104) were not distinguishable by anatomic location based on overall survival (
Discussion
We performed a comprehensive molecular and genomic characterization of 104 surgically resected CCAs. Our 238-gene classifier identified a high-risk group of patients with CCA, significantly differentiating patients according to overall and recurrence-free survival independent of specific clinical subtypes. Reflecting the strength of the classifier, it could be further reduced to 36 genes, which differentiated individuals in outcome-linked categories with greater accuracy. A comparison with our
Acknowledgments
The authors thank Tanya Hoang (Laboratory of Experimental Carcinogenesis, National Cancer Institute) for laboratory assistance and Teresa Mettler (Mayo Clinic) for abstracting clinical data.
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Conflicts of interest The authors disclose no conflicts.
Funding Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institutes of Health grants CA100882 and CA128633 (to L.R.R.) and P30DK084567 (Mayo Clinic Center for Cell Signaling in Gastroenterology); and grant 271-070712 from the Danish Medical Research Council (to J.B.A.).