2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Low Expression of DDX60 Gene Might Associate with the Radiosensitivity for Patients with Breast Cancer

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          DEXD/H box helicase 60 (DDX60) is a new type of DEAD-box RNA helicase, which is induced to express after virus infection. It might involve in antiviral immunity by promoting RIG-I-like receptor-mediated signal transduction. In addition, previous studies had shown that the expression of DDX60 is related to cancer, but there was still a lack of relevant research in breast cancer. In this study, we used the information of patients with breast cancer in the TCGA database for statistical analysis and found that the breast cancer patients with low expression of DDX60 exhibited radiosensitivity. Comparing the radiotherapy groups with the nonradiotherapy groups, for patients with low expression of DDX60, the adjusted hazard ratio (HR) values for radiotherapy were 0.244 (0.064–0.921) and 0.199 (0.062–0.646) in the training and validation datasets, with the p values 0.040 and 0.007, respectively. However, for patients with high expression of DDX60, the adjusted hazard ratio (HR) values were 3.582 (0.627–20.467) and 2.421 (0.460–12.773), with the p values 0.054 and 0.297, respectively. These results suggested that the expression of DDX60 might strongly associate with individualized radiosensitivity in patients with breast cancer.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: not found

          Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

          Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial.

            Postmastectomy radiotherapy is associated with a lower locoregional recurrence rate and improved disease-free and overall survival when combined with chemotherapy in premenopausal high-risk breast-cancer patients. However, whether the same benefits apply also in postmenopausal women treated with adjuvant tamoxifen for similar high-risk cancer is unclear. In a randomised trial among postmenopausal women who had undergone mastectomy, we compared adjuvant tamoxifen alone with tamoxifen plus postoperative radiotherapy. Between 1982 and 1990, postmenopausal women with high-risk breast cancer (stage II or III) were randomly assigned adjuvant tamoxifen (30 mg daily for 1 year) alone (689) or with postoperative radiotherapy to the chest wall and regional lymph nodes (686). Median follow-up was 123 months. The endpoints were first site of recurrence (locoregional recurrence, distant metastases, or both), and disease-free and overall survival. Locoregional recurrence occurred in 52 (8%) of the radiotherapy plus tamoxifen group and 242 (35%) of the tamoxifen only group (p<0.001). In total there were 321 (47%) and 411 (60%) recurrences, respectively. Disease-free survival was 36% in the radiotherapy plus tamoxifen group and 24% in the tamoxifen alone group (p<0.001). Overall survival was also higher in the radiotherapy group (385 vs 434 deaths; survival 45 vs 36% at 10 years, p=0.03). Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection, with 1 year of adjuvant tamoxifen treatment. Improved survival in high-risk breast cancer can best be achieved by a strategy of both locoregional and systemic tumour control.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1

              Epithelial-mesenchymal transition (EMT) is associated with characteristics of breast cancer stem cells, including chemoresistance and radioresistance. However, it is unclear whether EMT itself or specific EMT regulators play causal roles in these properties. Here we identify an EMT-inducing transcription factor, zinc finger E-box binding homeobox 1 (ZEB1), as a regulator of radiosensitivity and DNA damage response (DDR). Radioresistant subpopulations of breast cancer cells derived from ionizing radiation exhibit hyperactivation of ATM and upregulation of ZEB1, and ZEB1 promotes tumor cell radioresistance in vitro and in vivo. Mechanistically, ATM kinase phosphorylates and stabilizes ZEB1 in response to DNA damage, and ZEB1 in turn directly interacts with USP7 and enhances its ability to deubiquitinate and stabilize CHK1, thereby promoting homologous recombination-dependent DNA repair and resistance to radiation. These findings identify ZEB1 as an ATM substrate linking ATM to CHK1 and as the mechanism underlying the association between EMT and radioresistance.
                Bookmark

                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                JO
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2020
                20 July 2020
                : 2020
                : 8309492
                Affiliations
                1Department of Biostatistics, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
                2Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Soochow University, Suzhou 215123, China
                3State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China
                4Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou 215123, China
                5Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215123, China
                6Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou 215123, China
                Author notes

                Academic Editor: San-Lin You

                Author information
                https://orcid.org/0000-0003-1300-9533
                https://orcid.org/0000-0003-4981-3347
                Article
                10.1155/2020/8309492
                7387961
                caa5124d-2164-45b2-b77f-af57e5ffadba
                Copyright © 2020 Dongrun Xin et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 24 January 2020
                : 26 June 2020
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 81773541
                Award ID: 81573253
                Award ID: 81872552
                Award ID: U1967220
                Funded by: Soochow University
                Funded by: State Key Laboratory of Radiation Medicine and Protection
                Award ID: GZK1201919
                Funded by: Jiangsu Provincial Key Project in Research and Development of Advanced Clinical Technique
                Award ID: BL2018657
                Funded by: Undergraduate Training Program for Innovation and Entrepreneurship
                Award ID: 2019xj062
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

                Comments

                Comment on this article