An inflammatory response-related gene signature associated with immune status and prognosis of acute myeloid leukemia

Xin Wu; Shiqin Li; Dongjie Chen; Guiping Zheng; Zhaohua Zhang; Zian Li; Xiaoying Sun; Qiangqiang Zhao; Jingjuan Xu

An inflammatory response-related gene signature associated with immune status and prognosis of acute myeloid leukemia

Am J Transl Res. 2022 Jul 15;14(7):4898-4917. eCollection 2022.

Authors

Xin Wu¹, Shiqin Li², Dongjie Chen³, Guiping Zheng⁴, Zhaohua Zhang⁴, Zian Li⁵, Xiaoying Sun⁶, Qiangqiang Zhao⁴, Jingjuan Xu⁷

Affiliations

¹ Department of Spine Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
² Department of Cell Biology, School of Life Sciences, Central South University Changsha 410013, Hunan, China.
³ Department of Hepatopancreatobiliary Surgery, The Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
⁴ Department of Hematology, The Qinghai Provincial People's Hospital Xining 810007, Qinghai, China.
⁵ Department of Clinical Laboratory, Qinghai Provincial People's Hospital Xining 810007, Qinghai, China.
⁶ Department of Emergency, The Qinghai Provincial People's Hospital Xining 810007, China.
⁷ Department of Outpatient, The First People's Hospital of Changzhou Changzhou 213000, Jiangsu, China.

PMID: 35958446
PMCID: PMC9360836

Abstract

Objective: To determine the prognostic significance of inflammatory response-associated genes in acute myeloid leukemia (AML).

Methods: Transcriptomic profiles and related clinical information of AML patients were acquired from a public database. To establish a multi-gene prognosis signature, we performed least absolute shrinkage and selection operator Cox analysis for the TCGA cohort and evaluated the ICGC cohort for verification. Subsequently, Kaplan-Meier analysis was carried out to compare the overall survival (OS) rates between high- and low-risk groups. Biological function and single-sample gene set enrichment (ssGSEA) analyses were employed to investigate the association of risk score with immune status and the tumor microenvironment. Prognostic gene expression levels in AML samples and normal controls were confirmed by qRT-PCR and immunofluorescence.

Results: We identified a potential inflammatory response-related signature comprising 11 differentially expressed genes, including ACVR2A, CCL22, EBI3, EDN1, FFAR2, HRH1, ICOSLG, IL-10, INHBA, ITGB3, and LAMP3, and found that AML patients with high expression levels in the high-risk group had poor OS rates. Biological function analyses revealed that prognostic genes mainly participated in inflammation and immunity signaling pathways. Analyses of cancer-infiltrating immunocytes indicated that in high-risk patients, the immune suppressive microenvironment was significantly affected. The expression of the inflammation reaction-associated signature was found to be associated with susceptibility to chemotherapy. There was a significant difference in prognostic gene expression between AML and control tissues.

Conclusion: A novel inflammatory response-related signature was developed with 11 candidate genes to predict prognosis and immune status in AML patients.

Keywords: Acute myeloid leukemia; drug sensitivity; immune status; inflammatory response; overall survival; prognostic gene signature; tumor microenvironment.