A hypoxia risk signature for the tumor immune microenvironment evaluation and prognosis prediction in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is the most prevalent form of acute leukemia. Patients with AML often have poor clinical prognoses. Hypoxia can activate a series of immunosuppressive processes in tumors, resulting in diseases and poor clinical prognoses. However, how to evaluate the severity of hypoxia in tumor immune microenvironment remains unknown. In this study, we downloaded the profiles of RNA sequence and clinicopathological data of pediatric AML patients from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, as well as those of AML patients from Gene Expression Omnibus (GEO). In order to explore the immune microenvironment in AML, we established a risk signature to predict clinical prognosis. Our data showed that patients with high hypoxia risk score had shorter overall survival, indicating that higher hypoxia risk scores was significantly linked to immunosuppressive microenvironment in AML. Further analysis showed that the hypoxia could be used to serve as an independent prognostic indicator for AML patients. Moreover, we found gene sets enriched in high-risk AML group participated in the carcinogenesis. In summary, the established hypoxia-related risk model could act as an independent predictor for the clinical prognosis of AML, and also reflect the response intensity of the immune microenvironment in AML.

A comprehensive single-cell expression atlas of human AML leukemia-initiating cells unravels the contribution of HIF pathway and its therapeutic potential

“…A hypoxia risk signature with prognostic value has been proposed (73), linking high HIF expression to shorter overall survival, similar to other studies (29,72,74). Comparison of paired Dx-REL samples enables the analysis of both therapy naïve-and therapy-resistant LSCs, providing insights into their evolution within the same patient.…”

Novel Hypoxia-Associated Gene Signature Depicts Tumor Immune Microenvironment and Predicts Prognosis of Colon Cancer Patients

“…Our present work identified that hypoxia-related genes and the risk score model built on them were significantly correlated with the prognosis of CC patients. Similar results were found in ovarian cancer ( Chen et al, 2021 ), triple-negative breast cancer ( Yang et al, 2021a ), osteosarcoma in children ( Jiang et al, 2021a ), acute myeloid leukemia ( Jiang et al, 2021b ), and so on. It indicated that along with other factors, hypoxia might play an important role in the development and progression of cancer.…”

Establishment of Prognosis Model in Acute Myeloid Leukemia Based on Hypoxia Microenvironment, and Exploration of Hypoxia-Related Mechanisms

“…In this patient subgroup (ELN favorable–HPM high), representing 9.3% (37/397, only contains patients who had clear ELN2017 stratification) of the BEATAML1.0 cohort, their survival was similar to that of ELN intermediate/adverse-risk patients with HPM low-risk. To further evaluate the performance of the HPM, we compared our HPM with other gene expression based AML prognostic models, which were published within the last 5 years, including PMID29138577 ( Huang et al, 2017 ), PMID32268820 ( Zhang and Xiao, 2020 ), PMID29956722 ( Zhao et al, 2018 ), and PMID34282207 ( Jiang et al, 2021 ). Risk score was calculated based on formulas from the corresponding literatures.…”