Identification of a Mitochondria-Related Gene Signature to Predict the Prognosis in AML

Abstract

Mitochondria-related metabolic reprogramming plays a major role in the occurrence, development, drug resistance, and recurrence of acute myeloid leukemia (AML). However, the roles of mitochondria-related genes (MRGs) in the prognosis and immune microenvironment for AML patients remain largely unknown. In this study, by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, 4 MRGs’ (HPDL, CPT1A, IDH3A, and ETFB) signature was established that demonstrated good robustness in TARGET AML datasets. The univariate and multivariate Cox regression analyses both demonstrated that the MRG signature was a robust independent prognostic factor in overall survival prediction with high accuracy for AML patients. Based on the risk score calculated by the signature, samples were divided into high- and low-risk groups. Gene set enrichment analysis (GSEA) suggested that the MRG signature is involved in the immune-related pathways. Via immune infiltration analysis and immunosuppressive genes analysis, we found that MRG risk of AML patients was strikingly positively correlated with an immune cell infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused by immunosuppressive tumor microenvironment (TME). In summary, the signature based on MRGs could act as an independent risk factor for predicting the clinical prognosis of AML and could also reflect an association with the immunosuppressive microenvironment, providing a novel method for AML metabolic and immune therapy based on the regulation of mitochondrial function.

Identification and experimental validation of mitochondria-related genes biomarkers associated with immune infiltration for sepsis

“…In addition, after dividing sepsis patients into two groups using consensus clustering, we observed the effect of MiRGs on the immune microenvironment of patients with Sepsis. The effect of MiRGs on immune infiltration in other diseases has been reported ( 41 – 43 ). We have observed that DE-MiRG screened in sepsis is associated with neutrophil immune infiltration.…”

Integrated bioinformatic analysis of mitochondrial metabolism-related genes in acute myeloid leukemia

“…We then combined risk scores and clinical characteristics (age and gender) to develop a nomogram, indicating that risk score was an independent predictor. The predictive capability of our risk signature is equivalent to that of a signature including four genes ( 23 ) and a signature including six genes ( 22 ). However, our signature can better predict antitumor immune responses and promotes the finding of biological targets for immune treatments.…”

“…However, this study didn’t explore the relationship of TME and metabolism. In addition, another study found that four mitochondria-related genes (HPDL, CPT1A, IDH3A, and ETFB) influence the prognosis and BM microenvironment of AML patients ( 23 ). However, the bioinformatics study was validated based on a children cohort and relatively simple: no omics integration analysis, no somatic mutation assessment, or without experimental validation.…”

Breast Cancer Prognosis Prediction and Immune Pathway Molecular Analysis Based on Mitochondria-Related Genes

“…Not only the gene expression patterns, imaging data, clinical characteristics [ 17 ], radiomics results [ 18 ], or other variables can also be used to establish prognostic models. Mitochondria play an important role in different cancers; mitochondria-related genes had also been used to build prognostic models of other diseases, for example, acute myeloid leukemia [ 19 ]. But this thinking perspective seems did not attract researchers' attention in previous breast cancer studies.…”