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Aging-related genes related to the prognosis and the immune microenvironment of acute myeloid leukemia

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Abstract

Background

Acute myeloid leukemia (AML), one of the common malignancies of the hematologic system, has progressively increased in incidence. Aging is present in both normal tissues and the tumor microenvironment. However, the relationship between senescence and AML prognosis is still not elucidated.

Methods

In this study, RNA sequencing data of AML were obtained from TCGA, and prognostic prediction models were established by LASSO-Cox analysis. Differences in immune infiltration between the different risk groups were calculated using the CIBERSORT and ESTIMATE scoring methods. The KEGG and GO gene enrichment and GSEA enrichment were also used to enrich for differential pathways between the two groups. Subsequently, this study collected bone marrow samples from patients and healthy individuals to verify the differential expression of uncoupling protein 2 (UCP2) in different populations. Genipin, a UCP2 protein inhibitor, was also used to examine its effects on proliferation, cell cycle, and apoptosis in AML cell lines in vitro.

Results

It showed that aging-related genes (ARGs) expression was correlated with prognosis. And there was a significant difference in the abundance of immune microenvironment cells between the two groups of patients at high risk and low risk. Subsequently, UCP2 expression was found to be elevated in AML patients. Genipin inhibits UCP2 protein and suppresses the proliferation of AML cell lines in vitro.

Conclusion

ARGs can be used as a predictor of prognosis in AML patients. Moreover, suppressing UCP2 can reduce the proliferation of AML cell lines, alter their cell cycle, and promote apoptosis in vitro.

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Availability of data and material

The datasets generated during analyses in the current study are available in the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO).

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Acknowledgements

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

This work was supported by the major project of the Wenzhou Municipal Science and Technology Bureau (No. ZY2012013).

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Author notes

  1. Dongxu Gang and Yinyan Jiang have contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Dongxu Gang, Yinyan Jiang, Xiaofang Wang, Jifan Zhou, Xiaoyuan Zhang, Xiaoyu He, Rujiao Dong, Ziyang Huang & Songfu Jiang

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Contributions

DG: conceptualization, methodology, writing—original draft. YJ: conceptualization, methodology, writing—original draft. XW: formal analysis, investigation. JZ: data curation, visualization. XZ: methodology, visualization. XH: formal analysis, investigation. RD: data curation, writing—original draft. ZH: writing—review and editing, supervision. SJ: project administration, funding acquisition, writing—review and editing.

Corresponding authors

Correspondence to Ziyang Huang or Songfu Jiang.

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Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval

The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by the Ethic Committee in Clinical Research of The First Affiliated Hospital of Wenzhou Medical University (2021-063).

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Gang, D., Jiang, Y., Wang, X. et al. Aging-related genes related to the prognosis and the immune microenvironment of acute myeloid leukemia. Clin Transl Oncol 25, 2991–3005 (2023). https://doi.org/10.1007/s12094-023-03168-8

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