Transcriptome analysis of human colorectal cancer biopsies reveals extensive expression correlations among genes related to cell proliferation, lipid metabolism, immune response and collagen catabolism
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Lai Xu1,*, Rong Wang1,*, Joseph Ziegelbauer2, Wells W. Wu3, Rong-Fong Shen3, Hartmut Juhl4, Yaqin Zhang1, Lorraine Pelosof5 and Amy S. Rosenberg1
1Office of Biotechnology Products, CDER, FDA, Silver Spring, MD 20993, USA
2HIV/AIDS Malignancy Branch, NCI, Bethesda, MD 20892, USA
3Facility for Biotechnology Resources, CBER, FDA, Silver Spring, MD 20993, USA
4Indivumed GMBH, Hamburg 20251, Germany
5Office of Hematology and Oncology Products, CDER, FDA, Silver Spring, MD 20993, USA
*These authors have contributed equally to this work
Amy S. Rosenberg, email: amy.rosenberg@FDA.hhs.gov
Keywords: cell cycle, lipid metabolism, inflammation, collagen catabolism, gene co-expression network
Received: April 28, 2016 Accepted: July 12, 2017 Published: August 18, 2017
Precise characterization of biological processes critical to proliferation and metastasis of colorectal cancer should facilitate the development of diagnostic and prognostic biomarkers as well as novel treatments. Using mRNA-Seq, we examined the protein coding messenger RNA (mRNA) expression profiles across different histologically defined stages of primary colon cancers and compared them to their patient matched normal tissue controls. In comparing 79 colorectal cancers to their matched normal mucosa, tumors were distinguished from normal non-malignant tissues not only in the upregulation of biological processes pertaining to cell proliferation, inflammation, and tissue remodeling, but even more strikingly, in downregulated biological processes including fatty acid beta oxidization for ATP production and epithelial cell differentiation and function. A network analysis of deregulated genes revealed newly described cancer networks and putative hub genes.
Taken together, our findings suggest that, within an inflammatory microenvironment, invasive, dedifferentiated and rapidly dividing tumor cells divert the oxidation of fatty acids and lipids from energy production into lipid components of cell membranes and organelles to support tumor proliferation. A gene co-expression network analysis provides a clear and broad picture of biological pathways in tumors that may significantly enhance or supplant current histopathologic studies.
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