Lin Sheng-Yan, Hu Fei-Fei, Miao Ya-Ru, Hu Hui, Lei Qian, Zhang Qiong, Li Qiubai, Wang Hongxiang, Chen Zhichao, Guo An-Yuan
Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Bioinformatics and Systems Biology, Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Mol Ther Nucleic Acids. 2019 Dec 6;18:476-484. doi: 10.1016/j.omtn.2019.09.014. Epub 2019 Sep 23.
Cytogenetically normal acute myeloid leukemia (CN-AML) presents with diverse outcomes in different patients and is categorized as an intermediate prognosis group. It is important to identify prognostic factors for CN-AML risk stratification. In this study, using the TCGA CN-AML dataset, we found that the scavenger receptor stabilin-1 (STAB1) is a prognostic factor for poor outcomes and validated it in three other independent CN-AML datasets. The high STAB1 expression (STAB1) group had shorter event-free survival compared with the low STAB1 expression (STAB1) group in both the TCGA dataset (n = 79; p = 0.0478) and GEO: GSE6891 dataset (n = 187; p = 0.0354). Differential expression analysis between the STAB1 and STAB1 groups revealed that upregulated genes in the STAB1 group were enriched in pathways related to cell adhesion and migration and immune responses. We confirmed that STAB1 suppression inhibits cell growth in KG1a and NB4 leukemia cells. Expression correlation analyses between STAB1 and cancer drug targets suggested that patients in the STAB1 group are more sensitive to the BCL2 inhibitor venetoclax, and we confirmed it in cell lines. In conclusion, we identified STAB1 as a prognostic factor for CN-AML in multiple datasets, explored its underlying mechanism, and provided potential therapeutic indications.
细胞遗传学正常的急性髓系白血病（CN-AML）在不同患者中表现出不同的预后，被归类为预后中等的组。识别CN-AML风险分层的预后因素很重要。在本研究中，我们使用TCGA CN-AML数据集发现清道夫受体稳定素-1（STAB1）是预后不良的一个预后因素，并在其他三个独立的CN-AML数据集中对其进行了验证。在TCGA数据集（n = 79；p = 0.0478）和GEO：GSE6891数据集（n = 187；p = 0.0354）中，高STAB1表达（STAB1）组与低STAB1表达（STAB1）组相比，无事件生存期更短。STAB1和STAB1组之间的差异表达分析表明，STAB1组中上调的基因在与细胞粘附、迁移和免疫反应相关的途径中富集。我们证实STAB1抑制可抑制KG1a和NB4白血病细胞的生长。STAB1与癌症药物靶点之间的表达相关性分析表明，STAB1组患者对BCL2抑制剂维奈克拉更敏感，我们在细胞系中对此进行了证实。总之，我们在多个数据集中将STAB1鉴定为CN-AML的预后因素，探索了其潜在机制，并提供了潜在的治疗指征。
