Transcriptome analysis of human colorectal cancer biopsies reveals extensive expression correlations among genes related to cell proliferation, lipid metabolism, immune response and collagen catabolism

Lai Xu, Rong Wang, Joseph Ziegelbauer, Wells W. Wu, Rong Fong Shen, Hartmut Juhl, Yaqin Zhang, Lorraine Pelosof, Amy S. Rosenberg

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

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 nonmalignant 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.

Original languageEnglish (US)
Pages (from-to)74703-74719
Number of pages17
JournalOncotarget
Volume8
Issue number43
DOIs
StatePublished - 2017

Keywords

  • Cell cycle
  • Collagen catabolism
  • Gene co-expression network
  • Inflammation
  • Lipid metabolism

ASJC Scopus subject areas

  • Oncology

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