Identification of hub genes associated with adult acute myeloid leukemia progression through weighted gene co-expression network analysis

Acute myeloid leukemia (AML) is a malignancy of hematopoietic stem cells. Although many candidate genes such as CEBPA, FLT3, IDH1, and IDH2 have been associated with AML initiation and prognosis, the molecular mechanisms underlying this disease remain unclear. In this study, we used a systemic co-expression analysis method, namely weighted gene co-expression network analysis (WGCNA), to identify new candidate genes associated with adult AML progression and prognosis. We identified around 5,138 differentially expressed genes (DEGs) between AML samples (from The Cancer Genome Atlas database) and normal control samples (from the Genotype-Tissue Expression database). WGCNA identified nine co-expression modules with significant differences based on the DEGs. Among modules, the turquoise and blue ones were the most relevant to AML (P-value: turquoise 0, blue 4.64E-77). GO term and KEGG pathway analyses revealed that pathways that are commonly dysregulated in AML were all enriched in the blue and turquoise modules. A total of 15 hub genes were identified to be crucial for AML progression. PIVOT analysis revealed non-coding RNAs, transcriptional factors, and drugs associated with the hub genes. Finally, survival analysis revealed that one of the hub genes, CEACAM5, was significantly associated with AML prognosis and could serve as a potential target for AML treatment.