Background: This study aims to identify the hub genes and immune-related pathways in acute myeloid leukemia AML to provide new theories for immunotherapy. Methods: We use bioinformatics methods to find and verify the hub gene.
At the same time, we use the results of GSEA enrichment analysis to find immune-related mediators. Through Mendelian randomization MR analysis, on the one hand, we look for related immune cells, and on the other hand, we use it to determine the causal relationship among immune cells, immune mediators, and AML. Finally, in vitro experiments are conducted to further verify and improve the reliability and physiological functions of the hub gene and its immune-related pathways.
The latter three are positively correlated with the occurrence and development of AML. AML is a common acute leukemia that can occur in individuals of all ages 1 , 1. The diagnosis and treatment of AML often suffer from a lack of sensitive and specific biomarkers, with most patients diagnosed at intermediate or advanced stages 2. Furthermore, there are limited treatment options for AML, and it is common for drug resistance to develop 3 , 4.
Although treatment has been administered, the recurrence rate of patients with AML remains very high 5 , 6 , which leads to a very low overall survival rate 7 , 8. Therefore, identifying hub genes and associated mechanisms for pathogenesis, proliferation, and recurrence is crucial for early screening, accurate diagnosis, effective treatment strategies, and prognosis assessment 9 , The use of immune pathways to combat cancer cells has a history of a hundred years The first successful clinical application of immunotherapy is the use of allogeneic hematopoietic stem cell transplantation Studies have shown that it is of crucial importance to improve the immune efficacy and reduce toxic and side effects through immune analysis related to AML 15 — At present, there is still a great lack in this aspect 14 , Therefore, studying AML-related hub genes 19 and related immune pathways can provide valuable insights for AML in the aspect of immunotherapy In this study, our aim is to first screen for hub genes.
Through the screening and validation of differential genes, the hub genes related to the disease can be identified. And the GSEA analysis of all the co-expressed genes of hub genes can discover the pathways they regulate. By this means, in this study, we can identify the inflammatory factors regulated by hub genes. The immune infiltration analysis is then used to further confirm the immune association between hub genes and the disease. Afterwards, bulk MR is utilized to screen for immune cells, and mediation MR is employed to determine the relationship among inflammatory factors, immune cells and AML.
