Clinical Significance Of Expression Of Hsa-circ-0017884 In Acute And Chronic Myeloid Leukemia

Objective:Previous studies have revealed that up-regulated vimentin(VIM)gene plays an important role in various hematological malignancies.However,extremely few is known about the roles of Hsa-circ-0017884(a circular RNA of VIM),especially in myeloid leukemia.The focus of this study was to investigate the expression status of Hsa-circ-0017884 and further analyze its pathogenesis and clinical significance in acute myeloid leukemia(AML)and chronic myeloid leukemia(CML)patients.Additionally,the study further analyzed the correlation between Hsa-circ-0017884 and VIM gene expression in AML and explored its potential pathogenic mechanism.Methods:Bone marrow mononuclear cells from 42 healthy individuals,113 patients with newly diagnosed AML,and 54 CML patients were collected.Total RNA was isolated from bone marrow mononuclear cells,and total cellular RNA was reverse-transcribed into c DNA by using random primers.The transcript levels of Hsa-circ-0017884 in the collected healthy control samples,AML samples and CML patients were determined by real-time quantitative PCR(RQ-PCR)and then analyzed their clinical significance.The correlation between the expression level of Hsa-circ-0017884 in AML and the level of its parental gene VIM was also further analyzed.Results:1.Hsa-circ-0017884 expression level and clinical relevance in AML The expression level of Hsa-circ-0017884 was significantly up-regulated in AML compared with control(P<0.001)and was positively correlated with WBC count(r=0.259,P<0.001).ROC curve analysis indicated that the performance of Hsa-circ-0017884 expression could serve as a promising biomarker for differentiating AML patients from controls(AUC=0.741,95%CI: 0.657-0.825,P<0.001).In patients with AML,there were no significant differences in sex,age,hemoglobin,platelets,BM blasts,karyotypy classifications and nine gene mutations between the low Hsa-circ-0017884 expression group and high Hsa-circ-0017884 expression group(P>0.05).However,significant correlations of Hsa-circ-0017884 expression were found with WBC and FAB subtypes(P<0.05).Kaplan–Meier manifested that patients with high expression Hsa-circ-0017884 had significantly shorter OS(P<0.001)and LFS(P<0.001)than low expression Hsa-circ-0017884 patients in the whole cohort of AML patients.This poor prognosis associated with Hsa-circ-0017884over-expression was also observed in the Non-APL cohort of AML patients and CN-AML patients.Multivariate analysis and univariate analysis also disclosed that high Hsa-circ-0017884 expression was an independent prognostic factor in both OS and LFS among all AML patients.Notably,Pearson correlation analysis was applied to investigate the relationship between Hsa-circ-0017884 and the parental gene VIM expression in AML patients and demonstrated that there was a positive correlation between Hsa-circ-0017884 expression and VIM expression(r=0.439,P<0.001).2.Hsa-circ-0017884 expression level and clinical relevance in CML The level of Hsa-circ-0017884 was significantly up-regulated in AML patients compared with healthy controls(P < 0.001).ROC analysis showed that the expression level of Hsa-circ-0017884 can effectively distinguish the CML patients from healthy individuals(AUC=0.962,95%CI: 0.930-0.994).No significant association was observed between Hsa-circ-0017884 expression and laboratory features(including sex,age,WBC,Hb,PLT,karyotypy classifications,clinical stage and BCR-ABL)by analyzing the Hsa-circ-0017884 expression with clinical and laboratory characteristics.Conclusions:1.The over-expression Hsa-circ-0017884 is a common event in newly diagnosed AML,and Hsa-circ-0017884 gene may be a promising diagnostic,prognostic and initial therapeutic marker for AML patients.2.The expression of Hsa-circ-0017884 was positively correlated with the VIM expression in AML,suggesting that Hsa-circ-0017884 might promote the occurrence and development of AML by regulating the VIM gene.3.Hsa-circ-0017884 up-expression is a common molecular event in CML patients,while the high expression of Hsa-circ-0017884 gene has no significant correlation with CML disease progression.