The present study aimed to reveal the molecular characteristics induced by radiotherapy in rectal cancer at the transcriptome level. Microarray data (ID, GSE26027) downloaded from the Gene Expression Omnibus database were re‑analyzed to identify differentially expressed genes (DEGs) between rectal cancer tissues during and prior to radiotherapy. The DEGs were then inputted into the database for annotation, visualization and integrated discovery, an online tool to perform enrichment analyses, and into the search tool for the retrieval of interacting genes/proteins database to identify protein‑protein interactions (PPIs). Subsequently, a PPI network was constructed, which was screened for densely connected modules. Furthermore, protein domain enrichment analysis was performed. In total, 690 DEGs, including 179 upregulated and 511 downregulated DEGs, were found in rectal cancer tissues during and prior to radiotherapy. The upregulated DEGs were significantly enriched in ‘positive regulation of transport’ and ‘regulation of cardiac muscle contraction’, while the downregulated DEGs were most markedly enriched in ‘cell migration’, ‘cell‑cell signaling’, ‘extracellular matrix organization’ and ‘blood vessel development’, including prostaglandin-endoperoxide synthase 2, transforming growth factor β‑induced, 68 kDa endothelin receptor type A, brain‑derived neurotrophic factor, TIMP metallopeptidase inhibitor 1, and serpin family E member 1, which were the top 6 hub nodes in the PPI network. Furthermore, 2 protein domains were significantly enriched by PPI modules, including: The collagen triple helix repeat (CTHR) family members collagen type (COL) 5A2, COL9A3, COL6A3, COL21A1, COL5A3, COL11A1, COL7A1 and CTHR‑containing‑1; and the olfactory receptor family (OR) members OR7E24, OR7A17, OR6A2, OR1F1, OR10H3 and OR7A10. A total of 7 upregulated DEGs were characterized as tumor suppressor genes, and 8 downregulated DEGs were characterized as oncogenes. The biological processes or protein domains enriched by upregulated or downregulated DEGs may improve the understanding of molecular characteristics in response to radiotherapy.

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