Supervised learning based on tumor imaging and biopsy transcriptomics predicts response of hepatocellular carcinoma to transarterial chemoembolization.

Journal: Cell reports. Medicine
Published Date:

Abstract

Although transarterial chemoembolization (TACE) is the most widely used treatment for intermediate-stage, unresectable hepatocellular carcinoma (HCC), it is only effective in a subset of patients. In this study, we combine clinical, radiological, and genomics data in supervised machine-learning models toward the development of a clinically applicable predictive classifier of response to TACE in HCC patients. Our study consists of a discovery cohort of 33 tumors through which we identify predictive biomarkers, which are confirmed in a validation cohort. We find that radiological assessment of tumor area and several transcriptomic signatures, primarily the expression of FAM111B and HPRT1, are most predictive of response to TACE. Logistic regression decision support models consisting of tumor area and RNA-seq gene expression estimates for FAM111B and HPRT1 yield a predictive accuracy of ∼90%. Reverse transcription droplet digital PCR (RT-ddPCR) confirms these genes in combination with tumor area as a predictive classifier for response to TACE.

Authors

  • Tuyana Boldanova
    Division of Gastroenterology and Hepatology, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
  • Geoffrey Fucile
    sciCORE Center for Scientific Computing, University of Basel, Basel, Switzerland.
  • Jan Vosshenrich
    Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland.
  • Aleksei Suslov
    Hepatology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
  • Caner Ercan
    Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Mairene Coto-Llerena
    Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Luigi M Terracciano
    Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Christoph J Zech
    Radiology and Nuclear Medicine, University Hospital Basel, Basel, Switzerland.
  • Daniel T Boll
  • Stefan Wieland
    Hepatology, Department of Biomedicine, University Hospital and University of Basel, Basel, Switzerland.
  • Markus H Heim
    Division of Gastroenterology and Hepatology, Clarunis, University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.