Download Identification of potential biomarker genes relating to radiation

Identification of potential biomarker genes relating to radiation sensitivity of cancer patients treated
with radiotherapy
Radiation is currently one of the most common treatments for all types of cancer patients
(about 60-70% of all cancer cases will be treated with radiation within the time course of therapy). A
significant proportion of patients treated with radiation will exhibit a variety of adverse toxic effects
ranging from mild ones like fatigue, up to severe ones like pneumonitis and even death or secondary
primary cancer. One of the most current challenges in radiation therapy is to secure effective tumor
treatment and at the same time increase disease-free survival for the patients with minimum side
effects from radiation. Different lines of evidence suggest the involvement of inflammation and
oxidative stress to be the main contributors of radiation late effects.
Our hypothesis is that the expression of a series of genes in blood cells associates with the
radiation sensitivity of human cancer patients. Thus the identification of such genes will help us create a
library of prognostic biomarkers for patients undergoing radiation therapy and optimize clinical
protocols to achieve personalized therapeutic regime.
METHOD
Raw data from different projects were downloaded from GEO public microarray database. These
data were background corrected, log2 transformed and quantile normalized, using packages (such as
limma) from Bioconductor suite (an open source, open development software project to provide tools
for the analysis and comprehension of high-throughput genomic data, based primarily on the R
programming language).
RESULTS
In a project among patients with breast or head and neck cancer (GSE40640), patients were
categorized as normal reactive or sensitive after being irradiated for the first time. Blood samples of
these patients were collected two to three years after their first irradiation session. Immortalized cell
lines were produced from every blood sample. The cell lines were irradiated (non-irradiated cells were
used as controls) and the gene expression of both irradiated and non-irradiated cells was determined
using microarrays. Our analysis indicated that there were no noticeable differences between the blood
samples of sensitive or normal reactive patients. What we noticed, though, was that around 50 genes
were differentially expressed between treated and untreated blood samples.
FUTURE PLANS
We are planning to compare the genes found in this project with the ones found in others. Our
ultimate goal is to identify common genes which are differentially expressed among many projects.
Towards that end, we will create a gene library, and a meta-analysis may be applied in order to gain
further insights into the synergistic pathways from different genes or group of genes.
Sensitive vs Normal Reactive for Treatment 5Gy
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