Background: Radiotherapy-associated secondary cancer is an important issue for the treatment of breast cancer (BCa). This study aimed to investigate the molecular mechanism and genetic risk factors for radiation-associated secondary diseases in BCa.
Methods: The differentially expressed genes (DEGs) between preradiation and postradiation BCa samples in the GSE65505 dataset were obtained. The pathways related to the radiation-associated DEGs in the protein-protein interaction (PPI) network modules were identified. miRNAs targeted to the key genes in the PPI network were identified, and their association with BCa prognosis was analyzed.
Results: A total of 136 radiation-associated DEGs preradiation and postradiation BCa samples were screened out. The PPI network consisted of a significant module that consisted of 21 upregulated DEGs that were associated with "hsa04512: ECM-receptor interaction," "hsa04151: PI3K-Akt signaling pathway," and "hsa04115: p53 signaling pathway." Sixteen DEGs, including three collagen genes collagen type I alpha 1 chain (COL1A1), COL3A1, and COL1A2, were enriched in 17 radiation-associated pathways. The three genes were upregulated in BCa tissues compared with controls and were also elevated by radiation. They were targeted by hsa-miR-29a/c, and the expression levels of hsa-miR-29a/c were associated with a poor prognosis of BCa.
Conclusions: The upregulation of COL1A1, COL3A1, and COL1A2 might be genetic risk factors for radiation-associated secondary diseases in BCa.
Keywords: Type I collagen; Type III collagen; breast cancer; radiotherapy; secondary cancer.
© 2022 Guorong Yao et al., published by De Gruyter.