Publication: Determination of candidate biomarkers through differential interactome in colorectal adenocarcinoma
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Date
2019-10-17
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Abstract
Colorectal cancer is one of the most lethal types of cancers common
in both men and women. According to the data base published by
the International Agency for Research on Cancer, colorectal cancer is
the third most common type of cancer found in Turkey and worldwide
[1]. The high heterogeneity of colorectal cancer leads to difficulties
explaining the biology and behavior of this cancer. The aim of this
study is to identify prognostic biomarkers and potential therapeutics
for colorectal cancer using the protein interactions differentiated
among healthy and tumor groups. Among this purpose at first stage,
the differential protein-protein interactions (dPPIs) were identified by
using “Differential Interactome” algorithm[2] which is published by our
research group. Two independent data sets were obtained from “The
Cancer Genome Atlas (TCGA)” containing 644 tumor samples and 51
normal samples and “Gene Expression Omnibus (GEO)” containing
32 tumor samples and 32 normal samples. As a result of differential
interactome analysis, significant dPPIs were determined (2434 dPPIs
in GEO data set, 1619 dPPIs in TCGA data set) and highly interacting
protein modules were identified. Principal Component Analysis for
diagnostic purpose and Kaplan-Meier analysis for prognostic purpose
were performed for each module. 16 modules were determined
significant having diagnostic potential while 6 modules were found
having prognostic potential. In addition common significant dPPIs in
both data sets were observed in point of drug repositioning and 6
dPPIs and 13 drug targets for these interactions were identified. By
using molecular dynamics simulations root mean square deviation
(RMSD) and root mean square fluctuation were taken as performance
metrics to perform further investigation in vitro cell culture. This
study will shed light on the identification of specific biomarkers and
drug targets for early detection, disease progression, and accurate
treatment, helping to understand some systems of colorectal cancer
by preventing high mortality.
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Keywords
Cancer, Differential Interactome, Molecular Dynamics
Citation
BEKLEN H., GULFİDAN G., TURANLI B., ÖZBEK SARICA P., YILMAZ B., ARĞA K. Y., \"Determination Of Candidate Biomarkers Through Differential Interactome in Colorectal Adenocarcinoma\", The 12th International Symposium on Health Informatics and Bioinformatics (HIBIT 2019), İzmir, Türkiye, 17 - 19 Ekim 2019