Oncotarget

Research Papers:

Modularity of the metabolic gene network as a prognostic biomarker for hepatocellular carcinoma

Fengdan Ye, Dongya Jia, Mingyang Lu, Herbert Levine and Michael W. Deem _

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Oncotarget. 2018; 9:15015-15026. https://doi.org/10.18632/oncotarget.24551

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Abstract

Fengdan Ye1,2,*, Dongya Jia2,3,*, Mingyang Lu4, Herbert Levine1,2,5,6 and Michael W. Deem1,2,3,5

1Department of Physics and Astronomy, Rice University, Houston, TX 77005, USA

2Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA

3Program in Systems, Synthetic and Physical Biology, Rice University, Houston, TX 77005, USA

4The Jackson Laboratory, Bar Harbor, ME 04609, USA

5Department of Bioengineering, Rice University, Houston, TX 77005, USA

6Department of Biosciences, Rice University, Houston, TX 77005, USA

*Co-first authorship

Correspondence to:

Michael W. Deem, email: mwdeem@rice.edu

Herbert Levine, email: herbert.levine@rice.edu

Keywords: modularity; metabolism; hepatocellular carcinoma; HCC; prognosis

Received: September 22, 2017     Accepted: February 10, 2018     Epub: February 22, 2018     Published: March 13, 2018

ABSTRACT

Abnormal metabolism is an emerging hallmark of cancer. Cancer cells utilize both aerobic glycolysis and oxidative phosphorylation (OXPHOS) for energy production and biomass synthesis. Understanding the metabolic reprogramming in cancer can help design therapies to target metabolism and thereby to improve prognosis. We have previously argued that more malignant tumors are usually characterized by a more modular expression pattern of cancer-associated genes. In this work, we analyzed the expression patterns of metabolism genes in terms of modularity for 371 hepatocellular carcinoma (HCC) samples from the Cancer Genome Atlas (TCGA). We found that higher modularity significantly correlated with glycolytic phenotype, later tumor stages, higher metastatic potential, and cancer recurrence, all of which contributed to poorer prognosis. Among patients with recurred tumors, we found the correlation of higher modularity with worse prognosis during early to mid-progression. Furthermore, we developed metrics to calculate individual modularity, which was shown to be predictive of cancer recurrence and patients’ survival and therefore may serve as a prognostic biomarker. Our overall conclusion is that more aggressive HCC tumors, as judged by decreased host survival probability, had more modular expression patterns of metabolic genes. These results may be used to identify cancer driver genes and for drug design.


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