ESTRO 2024 - Abstract Book

S5321

Radiobiology - Tumour biology

ESTRO 2024

1 Tarbiat-Modarres Univerity, Medical Physics, Tehran, Iran, Islamic Republic of. 2 Universitätsmedizin Mannheim, Department of Radiation Oncology, Mannheim, Germany. 3 Tehran University, Artificial intelligence, Tehran, Iran, Islamic Republic of. 4 Monash University, Department of Biochemistry and Molecular Biology, Victoria, Australia. 5 Islamic-Azad University- pharmaceutical branch, Department of bioinformatics and biotechnology, Tehran, Iran, Islamic Republic of. 6 Shahid-Beheshti university of medical sciences, Department of Radiation Oncology, Tehran, Iran, Islamic Republic of

Purpose/Objective:

In many cancers, side population (SP) cells demonstrate characteristics of cancer stem cells (CSCs), share tumor initiating capacity and are resistant to chemotherapeutic drugs. In this study, we explored over-expression of hub genes in clusters of SP cells in human pancreatic cancer using bioinformatics and system biology analysis and whether its gene expression analysis is associated with radioresistant characteristics.

Material/Methods:

A microarray dataset (GSE42404) was downloaded from the gene expression omnibus (GEO) database containing four main population (MP) and four side population (SP) pancreatic ductal adenocarcinoma samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analysis were performed. Cytoscape and Gephi software, and the EnrichR database were used for the protein-protein interaction (PPI) network, and cluster analysis of up-regulated differential expressed genes (uDEGs). Survival information was analyzed using the Kaplan-Meier plotter.

Results:

A total of 5001 DEGs consisting of 1075 up-regulated genes were obtained. The PPI network and Gephi results showed that the top nine highly expressed hub genes are, INS, ATM, ESR1, DCN, KDR, COL2A1, THBS1, FGFR1, LOX with the highest eigen-centrality, degree centrality, betweenness centrality, and closeness centrality. Hubs of hubs genes were divided into five modules in cluster analysis with a total of 168 genes in which the hub genes of each cluster were INS in cluster zero, ATM in cluster one, SNAP25 in cluster two, DCN in cluster three, and SOCS2 in cluster four based on betweenness centrality. KEGG pathway enrichment analysis suggested that upregulated hub genes in all five clusters were significantly enriched in the PPAR signaling pathway, homologous recombination, GABAergic synapse, ECM receptor interaction, and insulin signaling pathway in clusters zero to four, respectively. In addition, GO pathway enrichment analysis suggested that overexpressed DEGs significantly enriched in the regulation of fatty acid metabolic process (GO:0019217), double-strand break repair (GO:0006302), regulation of peptide hormone secretion (GO:0090276), extracellular matrix organization (GO:0030198), and regulation of small GTPase mediated signal transduction (GO:0051056) in clusters zero to four, respectively. Survival analysis based on the GEPIA database found that the expression of ATM, DCN, and COL2A1 significantly predicted lower overall survival in pancreatic adenocarcinoma cancer. At last, the most significant hub gene and signaling pathway is the ATM gene and double strand break repair, which illustrate the positive radioresistant correlation of side population pancreatic cancer cells.

Conclusion: