High BMI1 Expression with Low CD8+ and CD4+ T Cell Activity Could Promote Breast Cancer Cell Survival: A Machine Learning Approach

Journal of Personalized Medicine

卷:11

Byoung Kwan Son¹  Mi Jung Kwon²  Kyueng-Whan Min³  Dong-Hoon Kim⁴  Yumin Chung⁴  Seoung Wan Chae⁴  Sung-Im Do⁴ 

[1] Department of Internal Medicine, Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Uijeongbu 11749, Korea;

[2] Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Korea;

[3] Department of Pathology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri 11923, Korea;

[4] Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine, Seoul 03181, Korea;

关键词: BMI1;    breast neoplasms;    survival;    gene;    machine learning;   

DOI  :  10.3390/jpm11080739

来源: DOAJ

【 摘 要 】

BMI1 is known to play a key role in the regulation of stem cell self-renewal in both endogenous and cancer stem cells. High BMI1 expression has been associated with poor prognosis in a variety of human tumors. The aim of this study was to reveal the correlations of BMI1 with survival rates, genetic alterations, and immune activities, and to validate the results using machine learning. We investigated the survival rates according to BMI1 expression in 389 and 789 breast cancer patients from Kangbuk Samsung Medical Center (KBSMC) and The Cancer Genome Atlas, respectively. We performed gene set enrichment analysis (GSEA) with pathway-based network analysis, investigated the immune response, and performed in vitro drug screening assays. The survival prediction model was evaluated through a gradient boosting machine (GBM) approach incorporating BMI1. High BMI1 expression was correlated with poor survival in patients with breast cancer. In GSEA and in in silico flow cytometry, high BMI1 expression was associated with factors indicating a weak immune response, such as decreased CD8+ T cell and CD4+ T cell counts. In pathway-based network analysis, BMI1 was directly linked to transcriptional regulation and indirectly linked to inflammatory response pathways, etc. The GBM model incorporating BMI1 showed improved prognostic performance compared with the model without BMI1. We identified telomerase inhibitor IX, a drug with potent activity against breast cancer cell lines with high BMI1 expression. We suggest that high BMI1 expression could be a therapeutic target in breast cancer. These results could contribute to the design of future experimental research and drug development programs for breast cancer.

【 授权许可】

Unknown