Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach.
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ABSTRACT: Background
Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders.Results
This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten publicly available microarray datasets were analyzed and seven potential biomarkers were identified from the list of differentially expressed genes having a p value?ConclusionThe integrated pathway analysis indicated the role of these genes in important physiological responses, such as cell cycle regulation, WNT, hedgehog, MAPK, and calcium signaling pathways during colorectal cancer. These pathways are involved in cell proliferation, chemotaxis, cellular growth, differentiation, tissue patterning, and cytokine production. The study shows the regulatory role of these genes in colorectal cancer and the pathways that can be effected after the dysregulation of these genes.
SUBMITTER: Ilyas U
PROVIDER: S-EPMC7278058 | biostudies-literature | 2020 Dec
REPOSITORIES: biostudies-literature
Publications
Genome wide meta-analysis of cDNA datasets reveals new target gene signatures of colorectal cancer based on systems biology approach.
Ilyas Umair U Zaman Shaiq Uz SU Altaf Reem R Nadeem Humaira H Muhammad Syed Aun SA
Journal of biological research (Thessalonike, Greece) 20200608
<h4>Background</h4>Colorectal cancer is known to be the most common type of cancer worldwide with high disease-related mortality. It is the third most common cancer in men and women and is the second major cause of death globally due to cancer. It is a complicated and fatal disease comprising of a group of molecular heterogeneous disorders.<h4>Results</h4>This study identifies the potential biomarkers of CRC through differentially expressed analysis, system biology, and proteomic analysis. Ten p ...[more]
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Project description:Background Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The survival rate of patients with metastatic disease remains very dismal. Nevertheless, metastasis is a complex process and a single-level analysis is not likely to identify its key biological determinants. In this study, we used a systems biology approach to identify common metastatic pathways that are jointly supported by both mRNA and protein expression data in two distinct human metastatic OS models. Results mRNA expression microarray and N-linked glycoproteomic analyses were performed on two commonly used isogenic pairs of human metastatic OS cell lines, namely HOS/143B and SaOS-2/LM7. Pathway analysis of the differentially regulated genes and glycoproteins separately revealed pathways associated to metastasis including cell cycle regulation, immune response, and epithelial-to-mesenchymal-transition. However, no common significant pathway was found at both genomic and proteomic levels between the two metastatic models, suggesting a very different biological nature of the cell lines. To address this issue, we used a topological significance analysis based on a “shortest path” algorithm to identify topological nodes, which uncovered additional biological information with respect to the genomic and glycoproteomic profiles but remained hidden from the direct analyses. Pathway analysis of the significant topological nodes revealed a striking concordance between the models and identified significant common pathways, including “Cytoskeleton remodeling/TGF/WNT”, “Cytoskeleton remodeling/Cytoskeleton remodeling”, and “Cell adhesion/Chemokines and adhesion”. Of these, the “Cytoskeleton remodeling/TGF/WNT” was the top ranked common pathway from the topological analysis of the genomic and proteomic profiles in the two metastatic models. The up-regulation of proteins in the “Cytoskeleton remodeling/TGF/WNT” pathway in the SaOS-2/LM7 and HOS/143B models was further validated using an orthogonal Reverse Phase Protein Array platform. Conclusions In this study, we used a systems biology approach by integrating genomic and proteomic data to identify key and common metastatic mechanisms in OS. The use of the topological analysis revealed hidden biological pathways that are known to play critical roles in metastasis. Wnt signaling has been previously implicated in OS and other tumors, and inhibitors of Wnt signaling pathways are available for clinical testing. Further characterization of this common pathway and other topological pathways identified from this study may lead to a novel therapeutic strategy for the treatment of metastatic OS.
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