Key immune-related gene ITGB2 as a prognostic signature for acute myeloid leukemia

Autor:	Ming-Yue Xiong, Jie Wei, Yan Huang, Si-Nian Li, Donghong Deng, Xiang-You Yao, Xunjun Huang, Zhi-Ning Huang, Dalang Fang, Weijie Zhou, Peng Cheng
Rok vydání:	2021
Předmět:	Oncology medicine.medical_specialty business.industry Bortezomib Myeloid leukemia General Medicine Axitinib Docetaxel hemic and lymphatic diseases Internal medicine medicine Cytarabine Biomarker (medicine) Original Article business neoplasms Bosutinib IRGs medicine.drug
Zdroj:	Ann Transl Med
ISSN:	2305-5847 2305-5839
DOI:	10.21037/atm-21-3641
Popis:	Background The tumor microenvironment (TME) has an essential role in tumorigenesis, progression, and therapeutic response in many cancers. Currently, the role of TME in acute myeloid leukemia (AML) is unclear. This study investigated the correlation between immune-related genes and prognosis in AML patients. Methods Transcriptome RNA-Seq data for 151 AML samples were downloaded from TCGA database (https://portal.gdc.cancer.gov/), and the immune related genes (irgs) were selected from Immport database. Bioinformatics screening was used to identify irgs for AML, and genes with a critical role in the prognosis of AML were selected for further analysis. To confirm the prognostic role of irgs in AML, we undertook protein-protein interaction (PPI) network analysis of the top 30 interacting genes. We then investigated associations between immune cell infiltration and prognosis in AML patients. Immunohistochemistry was used to validate protein expression levels between AML and normal bone marrow samples. Analysis of the drug sensitivity of the selected gene was then performed. Results The integrin lymphocyte function-associated antigen 1 (CD11A/CD18; ITGAL/ITGB2) was identified as the key immune-related gene that significantly influenced prognosis in AML patients. Overexpression of ITGB2 indicated poor prognosis in AML patients (P=0.007). Risk modeling indicated that a high-risk score led to poor outcomes (P=3.076e-08) in AML patients. The risk model showed accuracy for predicting prognosis in AML patients, with area under curve (AUC) at 1 year, 0.816; AUC at 3 years, 0.82; and AUC at 5 years, 0.875. In addition, we found that ITGB2 had a powerful influence on immune cell infiltration into AML TME. The results of immunohistochemistry showed that AML patients had significantly higher ITGB2 protein expression than normal samples. The AML patients were divided into 2 groups based on ITGB2 risk scores. Drug sensitivity test results indicated that the high-risk group was sensitive to cytarabine, axitinib, bosutinib, and docetaxel, but resistant to cisplatin and bortezomib. Conclusions In the present study, we found that ITGB2 may be able to serve as a biomarker for assessing prognosis and drug sensitivity in AML patients.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3b7fb6f7cf10554e5ad1e86d353304c https://doi.org/10.21037/atm-21-3641 Zobrazit plný text záznamu