A novel kinase-related gene signature predicts the survival and therapeutic responses of Acute Myeloid Leukemia

Abstract Background Acute Myeloid Leukemia (AML) is a malignant blood disease with a poor prognosis. Kinase plays an important role in the occurrence and development of malignant tumors. However, the prognostic value of the kinase-related genes in AML is still unclear. Method The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and Beat-AML cohorts in the cbioportal database. We identified 538 kinase-related genes through the published article. Univariate Cox regression was used to analyze the association of kinase-related genes with overall survival (OS). The Least Absolute Shrinkage and Selection Operator (LASSO) was used to construct a kinase-related genes risk model for AML patients. The prognostic values of the model were validated via Kaplan‒Meier curves and Receiver Operating Characteristic (ROC). A nomogram, integrating clinical information and prognostic scores of patients, was constructed using multivariate logistic regression and Cox proportional hazards regression models. Gene Ontology (GO) and Gene Set Enrichment Analysis（GSEA）were referenced to identify multiple important biological functions and signaling pathways related to differentially expressed kinases between the low-risk and high-risk groups. The CIBERSORT algorithm explored the relationship of the immune microenvironment for AML. The oncoPredict package was adopted to calculate the IC50 of drugs for treating AML. Results Nine kinase-related genes—CDK11B, CDK18, LTK, PRKCE, STK10, PIM1, TLK2, LMTK2, and PTK—were identified to establish a prognostic model of AML. Patients in the high-risk group showed a poor prognosis (p< 0.001), which was validated in the Beat-AML database. The enrichment analyses revealed a multitude of biological pathways that are significantly associated with cancer. The kinase-related genes model was significantly associated with the immune microenvironment of AML， TKI inhibitor，CDK 9 inhibitor，BTK inhibitor, and CDK 4/6 inhibitor were found to be advantageous for high-risk groups. Conclusion In summary, a prognostic model including 9 kinase-related genes was constructed for AML patients，and the risk model's predictive performance and screened potential treatment drugs were analyzed.