Pan-cancer analysis of DDIT4 identifying its prognostic value and function in acute myeloid leukemia

Background: Acute myeloid leukemia (AML) is a hematological malignancy derived from the accumulation of abnormal proliferation of infantile leukocytes in the hematopoietic system. DNA-damage-inducible transcript 4 (DDIT4) acting as a negative regulator of rapamycin inhibitor is involved in various cellular functions. Many studies have suggested that DDIT4 plays a key role in tumorigenesis. However, the role of DDIT4 in AML has been poorly studied.

Method: In this study, we analyzed the expression of DDIT4 in AML patients using The Cancer Genome Atlas and real-time polymerase chain reaction. The Chi-square test was used to assess the correlation between DDIT4 and clinical characters in AML patients. Loss-of-function experiments were implemented to investigate the role of DDIT4 in AML carcinogenesis. The R package was applied to evaluate the correlation between DDIT4 expression and immune cells.

Results: Results showed that the expression of DDIT4 was associated with Age, Cytogenetic risk, Cytogenetics and OS event. Moreover, high expression of DDIT4 led to a terrible prognosis. KEGG analysis showed that differently expressed genes (DEGs) were involved in the PI3-Akt signaling pathway. GSEA enrichment analysis displayed DEGs were correlated with apoptosis. Functional experiments presented that knocking down DDIT4 suppressed cell cycle transition/proliferation and facilitated apoptosis. In addition, DDIT4 is associated with immune infiltration.

Conclusion: Our research verified that DDIT4 can be used as a prognostic marker and a potential therapeutic target for AML.