Genome-Scale Metabolic Modeling of Glioblastoma Reveals Promising Targets for Drug Development

• Glioblastoma (GBM) is an aggressive type of brain cancer with a poor prognosis for affected patients. The current line of treatment only gives the patients a survival time of on average 15 months. In this work, we use genome-scale metabolic models (GEMs) together with other systems biology tools to examine the global transcriptomics-data of GBM-patients obtained from The Cancer Genome Atlas (TCGA). We reveal the molecular mechanisms underlying GBM and identify potential therapeutic targets for effective treatment of patients. The work presented consists of two main parts. The first part stratifies the patients into two groups, high and low survival, and compares their gene expression. The second part uses GBM and healthy brain tissue GEMs to simulate gene knockout in a GBM cell model to find potential therapeutic targets and predict their side effect in healthy brain tissue. We (1) find that genes upregulated in the patients with low survival are linked to various stages of the glioma invasion process, and (2) identify five essential genes for GBM, whose inhibition is non-toxic to healthy brain tissue, therefore promising to investigate further as therapeutic targets.

Subject headings

NATURVETENSKAP  -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)

NATURVETENSKAP  -- Biologi -- Genetik (hsv//swe)

NATURAL SCIENCES  -- Biological Sciences -- Genetics (hsv//eng)

Keyword

GBM

GEMs

genome-scale metabolic models

glioblastoma

systems biology

gelatinase A

gelatinase B

phosphatidylinositol 3

4

5 trisphosphate 3 phosphatase

protein p53

Article

brain tissue

cancer staging

cancer survival

clinical trial (topic)

drug development

extracellular matrix

gene expression

gene knockout

genome

human

RNA sequence

transcriptomics

tumor invasion

upregulation

Publication and Content Type

ref (subject category)

art (subject category)