Identification of STAB1 in Multiple Datasets as a Prognostic Factor for Cytogenetically Normal AML: Mechanism and Drug Indications

Sheng-Yan Lin; Fei-Fei Hu; Ya-Ru Miao; Hui Hu; Qian Lei; Qiong Zhang; Qiubai Li; Hongxiang Wang; Zhichao Chen; An-Yuan Guo

doi:10.1016/j.omtn.2019.09.014

Identification of STAB1 in Multiple Datasets as a Prognostic Factor for Cytogenetically Normal AML: Mechanism and Drug Indications

Mol Ther Nucleic Acids. 2019 Dec 6:18:476-484. doi: 10.1016/j.omtn.2019.09.014. Epub 2019 Sep 23.

Authors

Sheng-Yan Lin¹, Fei-Fei Hu¹, Ya-Ru Miao¹, Hui Hu¹, Qian Lei¹, Qiong Zhang¹, Qiubai Li², Hongxiang Wang³, Zhichao Chen⁴, An-Yuan Guo⁵

Affiliations

¹ 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.
² Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ Department of Hematology, Key Laboratory for Molecular Diagnosis of Hubei Province, Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
⁴ Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: chenzhichao@hust.edu.cn.
⁵ 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. Electronic address: guoay@hust.edu.cn.

Abstract

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^high) group had shorter event-free survival compared with the low STAB1 expression (STAB1^low) 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^high and STAB1^low groups revealed that upregulated genes in the STAB1^high 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^low 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.

Keywords: STAB1; cytogenetically normal acute myeloid leukemia; prognostic factor; therapeutic indications.