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. 2021 Oct;25(19):9331-9339.
doi: 10.1111/jcmm.16870. Epub 2021 Aug 25.

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

Shenghao Hua  1 , Tao Feng  1 , Lei Yin  1 , Qi Wang  1 , Xuejun Shao  1
Affiliations

NEDD9 overexpression: Prognostic and guidance value in acute myeloid leukaemia

Shenghao Hua et al. J Cell Mol Med. 2021 Oct.

Abstract

It has been demonstrated that neural precursor cell expressed developmentally downregulated protein (NEDD) plays crucial roles in tumorigenesis and may serve as potential biomarkers in cancer diagnosis and prognosis. However, few studies systematically investigated the expression of NEDD family members in acute myeloid leukaemia (AML). We systemically determined the expression of NEDD family members in AML and determined their clinical significance. We identified that NEDD9 expression was the only member among NEDD family which was significantly increased in AML. NEDD9 overexpression was more frequently classified as FAB-M4/M5 (p = 0.008 and 0.013, respectively), hardly as FAB-M2/M3. Moreover, NEDD9 overexpression was significantly associated with complex karyotype and TP53 mutation. The significant association between NEDD9 overexpression and survival was also observed in whole-cohort AML and non-M3 AML patients. Notably, AML patients with NEDD9 overexpression may benefit from hematopoietic stem cell transplantation (HSCT), whereas those cases without NEDD9 overexpression did not. Finally, a total of 822 mRNAs and 31 microRNAs were found to be differentially expressed between two groups. Among the microRNAs, miR-381 was also identified as a microRNA that could direct target NEDD9. Taken together, our findings demonstrated that NEDD9 overexpression is associated with genetic abnormalities as well as prognosis and might act as a potential biomarker guiding the choice between HSCT and chemotherapy in patients with AML after achieving complete remission.

Keywords: NEDD9; AML; expression; prognosis.

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Conflict of interest statement

The authors confirm that there are no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
NEDD expression in AML. (A): NEDD1 expression in AML from TCGA data sets using the GEPIA. (B): NEDD4 expression in AML from TCGA data sets using the GEPIA. (C): NEDD8 expression in AML from TCGA data sets using the GEPIA. (D): NEDD9 expression in AML from TCGA data sets using the GEPIA. The red column indicates AML, whereas the grey column indicates control
FIGURE 2
FIGURE 2
The associations of NEDD9 expression with FAB classifications and cytogenetic/genetic abnormalities in AML. (A): NEDD9 expression among FAB subtypes. p value indicates the comparison of all FAB subtypes using Kruskal–Wallis H test. (B): NEDD9 expression among different cytogenetics. p value indicates the comparison of all cytogenetics using Kruskal–Wallis H test. (C): NEDD9 expression in AML patients with and without TP53 mutations. (D): NEDD9 expression in AML patients with and without NRAS mutations
FIGURE 3
FIGURE 3
The impact of NEDD9 expression on survival of AML patients. (A): Kaplan‐Meier survival curves of overall survival in whole‐cohort AML. (B): Kaplan‐Meier survival curves of leukaemia‐free survival in whole‐cohort AML. (C): Kaplan‐Meier survival curves of overall survival in non‐M3 AML. (D): Kaplan‐Meier survival curves of leukaemia‐free survival in non‐M3 AML
FIGURE 4
FIGURE 4
The effect of HSCT on survival of AML patients among NEDD9 overexpression and underexpression groups. (A): Kaplan‐Meier survival curves of overall survival among whole‐cohort AML in NEDD9 underexpression group. (B): Kaplan–Meier survival curves of leukaemia‐free survival among whole‐cohort AML in NEDD9 underexpression group. (C): Kaplan‐Meier survival curves of overall survival among non‐M3 AML in NEDD9 underexpression group. (D): Kaplan‐Meier survival curves of leukaemia‐free survival among non‐M3 AML in NEDD9 underexpression group. (E): Kaplan‐Meier survival curves of overall survival among whole‐cohort AML in NEDD9 overexpression group. (F): Kaplan–Meier survival curves of leukaemia‐free survival among whole‐cohort AML in NEDD9 overexpression group. (G): Kaplan‐Meier survival curves of overall survival among non‐M3 AML in NEDD9 overexpression group. (H): Kaplan–Meier survival curves of leukaemia‐free survival among non‐M3 AML in NEDD9 overexpression group
FIGURE 5
FIGURE 5
Biological network of NEDD9 in AML. (A): Expression heatmap of differentially expressed mRNAs between AML patients with NEDD9 overexpression and underexpression groups. (B): Volcano plot of differentially expressed mRNAs between AML patients with NEDD9 overexpression and underexpression groups. (C): Gene Ontology analysis of differentially expressed mRNAs conducted using online website of STRING (http://string‐db.org). (D): Expression heatmap of differentially expressed microRNAs between AML patients with NEDD9 overexpression and underexpression groups. (E): Venn results of microRNAs which could target NEDD9 predicted by DIANA (http://diana.imis.athena‐innovation.gr/DianaTools/index.php?r=microT_CDS/index), miRDB (http://mirdb.org/miRDB/), TargetScan (http://www.targetscan.org/vert_72/) and starBase (http://starbase.sysu.edu.cn/)
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