Case-control Indian buffet process identifies biomarkers of response to Codrituzumab View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Melanie F. Pradier, Bernhard Reis, Lori Jukofsky, Francesca Milletti, Toshihiko Ohtomo, Fernando Perez-Cruz, Oscar Puig

ABSTRACT

BACKGROUND: Codrituzumab, a humanized monoclonal antibody against Glypican-3 (GPC3), which is expressed in hepatocellular carcinoma (HCC), was tested in a randomized phase II trial in advanced HCC patients who had failed prior systemic therapy. Biomarker analysis was performed to identify a responder population that benefits from treatment. METHODS: A novel statistical method based on the Indian buffet process (IBP) was used to identify biomarkers predictive of response to treatment with Codrituzumab. The IBP is a novel method that allows flexibility in analysis design, and which is sensitive to slight, but meaningful between-group differences in biomarkers in very complex datasets RESULTS: The IBP model identified several subpopulations of patients having defined biomarker values. Tumor necrosis and viable cell content in the tumor were identified as prognostic markers of disease progression, as were the well-known HCC prognostic markers of disease progression, alpha-fetoprotein and Glypican-3 expression. Predictive markers of treatment response included natural killer (NK) cell surface markers and parameters influencing NK cell activity, all related to the mechanism of action of this drug CONCLUSIONS: The Indian buffet process can be effectively used to detect statistically significant signals with high sensitivity in complex and noisy biological data TRIAL REGISTRATION: NCT01507168 , January 6, 2012. More... »

PAGES

278

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12885-019-5472-0

DOI

http://dx.doi.org/10.1186/s12885-019-5472-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113053552

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30922327


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