Abstract
BackgroundRadiotherapy-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.MethodsThe 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.ResultsA 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.ConclusionsThe upregulation of COL1A1, COL3A1, and COL1A2 might be genetic risk factors for radiation-associated secondary diseases in BCa.
Highlights
Breast cancer (BCa) is the most commonly diagnosed malignant cancer and the leading cause of cancer-related premature mortality in women worldwide [1]
A total of 405, 204, and 325 differentially expressed genes (DEGs) were identified in BCa tumor samples receiving 15 Gy, 18 Gy, and 21 Gy intensity-modulated radiotherapy in the GSE65505 dataset, respectively (Figure 1a)
The functional enrichment analysis of the 136 radiationassociated DEGs indicated that these genes were enriched into 563 biological processes that were associated with extracellular matrix (ECM) organization, inflammatory response, response to metal ion, neutrophil-mediated immunity, and cell chemotaxis, and 38 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways including advanced glycation end-receptor for dvanced glycation end products (AGE-RAGE) signaling pathway in diabetic complication, p53 signaling pathway, PI3K-Akt signaling pathway, and ECM–receptor interaction
Summary
Breast cancer (BCa) is the most commonly diagnosed malignant cancer and the leading cause of cancer-related premature mortality in women worldwide [1]. The treatment of BCa is still an important issue due to the high recurrence and mortality of this disease. Radiotherapy reduces BCa recurrence and death significantly [4,5,6]. There are increasing evidence showing that radiotherapy causes secondary cancers and heart diseases decades later [7,8,9,10]. Patients exposed to radiotherapy for prostate cancer and BCa had an overtime increased risk of bladder, colorectal, lung, and thyroid cancers compared with patients unexposed to radiotherapy [8,10]. The chest wall symptoms in BCa patients exposed to radiotherapy were worse than that of patients unexposed to radiotherapy [9]. Hodgkin lymphoma patients that were treated with chest radiotherapy have a high risk of BCa [11]. The molecular mechanisms of the pathogenesis of radiation-associated secondary cancers are not clear until now
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
