J Cancer 2021; 12(14):4229-4239. doi:10.7150/jca.50472

Research Paper

High Expression of RhoBTB3 Predicts Favorable Chemothrapy Outcomes in non-M3 Acute Myeloid Leukemia

Shuang-Hui Yang*, Wei Liu*, Jie Peng, Ya-Jing Xu, Yan-Feng Liu, Yan Li, Min-Yuan Peng, Zhao Ou-Yang, Cong Chen, En-Yi Liu

Department of Hematology, XiangYa Hospital, Central South University, XiangYa Road No.87, Changsha 410008, China.
*co-first authors.

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Citation:
Yang SH, Liu W, Peng J, Xu YJ, Liu YF, Li Y, Peng MY, Ou-Yang Z, Chen C, Liu EY. High Expression of RhoBTB3 Predicts Favorable Chemothrapy Outcomes in non-M3 Acute Myeloid Leukemia. J Cancer 2021; 12(14):4229-4239. doi:10.7150/jca.50472. Available from https://www.jcancer.org/v12p4229.htm

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Abstract

Background: The expression patterns and prognostic significance of the Rho family GTPases in acute myeloid leukemia have not been systematically studied yet.

Methods: In our study, we analyzed the expression patterns of 21 Rho family GTPases gene members in AML patients based on GEPIA database. 10 gene members with significant differential expression in AML tissue and healthy tissue were selected for subsequent research. Survival curve analysis in TCGA and GEO dataset preliminary showed that RhoBTB3 is related with the prognosis of non-M3 AML patients. The differential expression of RhoBTB3 on AML bone marrow and normal bone marrow was verified by RT-qPCR. We performed Kaplan-Meier survival analysis and Multivariate Cox analysis to assess the prognostic value of RhoBTB3 in non-M3 AML patients with different treatment regimens. Gene functional enrichment analysis of RhoBTB3 was performed using GO, KEGG and PPI network.

Results: The AML patients from TCGA database were partitioned into 2 groups based on different treatment regimens: chemotherapy group and allo-HSCT group. In chemotherapy group, patients with higher expression level of RhoBTB3 showed relatively longer OS and EFS, multivariate Cox analysis revealed high RhoBTB3 mRNA expression as an independent favorable prognostic factor. However, in allo-HSCT group, no significant difference of OS and EFS were found between RhoBTB3 high and low subgroups. Meanwhile, allo-HSCT could circumvent the unfavorable prognosis that was associated with downregulation of RhoBTB3. Functional enrichment analysis showed the association of RhoBTB3 expression with several fundamental physiological components and pathways, including extracellular matrix components, extracellular structure organization, and cytokine-cytokine receptor interaction.

Conclusions: Our study identified RhoBTB3 as a prognostic marker and may aid in the selection of the appropriate treatment options between chemotherapy and allo-HCST in non-M3 AML patients. Further researches are necessary to clarify the involvement of RhoBTB3 in the pathogenesis of AML.

Keywords: Rho family GTPases, RhoBTB3, acute myeloid leukemia, prognostic value, TCGA