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Sci Rep. 2019 Mar 4;9(1):3369. doi: 10.1038/s41598-019-39727-9.

NELFE-Dependent MYC Signature Identifies a Unique Cancer Subtype in Hepatocellular Carcinoma.

Author information

1
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States. hien.dang@jefferson.edu.
2
Department of Surgery, Division of Surgical Research, Thomas Jefferson University, Philadelphia, PA, United States. hien.dang@jefferson.edu.
3
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States.
4
Translational Research Unit, Chulabhorn Research Institute, Bangkok, 10210, Thailand.
5
Department of Systems Biology, Division of Cancer Medicine, UT MDACC, Houston, TX, United States.
6
Department of Surgery, Division of Transplantation, Thomas Jefferson University, Philadelphia, PA, United States.
7
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, United States. xw3u@nih.gov.

Abstract

The MYC oncogene is dysregulated in approximately 30% of liver cancer. In an effort to exploit MYC as a therapeutic target, including in hepatocellular carcinoma (HCC), strategies have been developed on the basis of MYC amplification or gene translocation. Due to the failure of these strategies to provide accurate diagnostics and prognostic value, we have developed a Negative Elongation Factor E (NELFE)-Dependent MYC Target (NDMT) gene signature. This signature, which consists of genes regulated by MYC and NELFE, an RNA binding protein that enhances MYC-induced hepatocarcinogenesis, is predictive of NELFE/MYC-driven tumors that would otherwise not be identified by gene amplification or translocation alone. We demonstrate the utility of the NDMT gene signature to predict a unique subtype of HCC, which is associated with a poor prognosis in three independent cohorts encompassing diverse etiologies, demographics, and viral status. The application of gene signatures, such as the NDMT signature, offers patients access to personalized risk assessments, which may be utilized to direct future care.

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