國家衛生研究院 NHRI:Item 3990099045/12776
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    題名: BMI1-KLF4 axis deficiency improves responses to neoadjuvant concurrent chemoradiotherapy in patients with rectal cancer
    作者: Hsu, YC;Luo, CW;Huang, WL;Wu, CC;Chou, CL;Chen, CI;Chang, SJ;Chai, CY;Wang, HC;Chen, TY;Li, CF;Pan, MR
    貢獻者: National Institute of Cancer Research
    摘要: PURPOSE: Neoadjuvant concurrent chemoradiotherapy (CCRT) is a gold standard treatment for patients with stage II/III rectal cancer. B-cell-specific Moloney murine leukemia virus insertion site 1 (BMI1) is a member of the polycomb group of proteins that are involved in regulating gene expression. High levels of BMI1 have been demonstrated to contribute to the malignant phenotypes of several cancers; however, its relevance in rectal cancer treated with CCRT is largely unknown. METHODS AND MATERIALS: We used two patient cohorts to address the clinical relevance of BMI1 in human cancers. In addition, HT-29 and HCT-116 cells were chosen as our in vitro models to verify the role of BMI1 in cell response to ionizing radiation. Stemness-related proteins were analyzed by western blotting and cell survival was determined using clonogenic assays. RESULTS: BMI1 overexpression was found to significantly correlate with advanced pre-treatment nodal status (N1-N2; p < 0.001), post-treatment tumor stage (T1-T2; p = 0.015), inferior tumor regression grade (p = 0.001), and also an independent prognosis factor in 172 rectal cancer patients receiving CCRT. Serial cell-based functional examination indicated that BMI1 deficiency sensitized cells to radiation treatment by modulating the gene expression of Kruppel-like factor 4 (KLF4) and enhanced radiosensitivity in microsatellite stable (MSS) colorectal cancers. Overexpression of KLF4 partially overcame BMI1-deficiency-mediated γ-H2AX expression after ionizing radiation exposure. Consistent with in vitro data, an analysis of an additional 30 rectal cancer tissue specimens revealed a positive correlation between BMI1 and KLF4 (p = 0.02). CONCLUSION: Higher levels of BMI1 are associated with poor therapeutic response and adverse outcomes in rectal cancer patients receiving CCRT.
    日期: 2020-08
    關聯: Radiotherapy and Oncology. 2020 Aug;149:249-258.
    Link to: http://dx.doi.org/10.1016/j.radonc.2020.06.023
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0167-8140&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000561731500048
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85087972048
    顯示於類別:[其他] 期刊論文

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