Wei Jie, Huang Xun-Jun, Huang Yan, Xiong Ming-Yue, Yao Xiang-You, Huang Zhi-Ning, Li Si-Nian, Zhou Wei-Jie, Fang Da-Lang, Deng Dong-Hong, Cheng Peng
Department of Hematology, Baise People's Hospital, Baise, China.
Department of Breast and Thyroid Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Ann Transl Med. 2021 Sep;9(17):1386. doi: 10.21037/atm-21-3641.
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.
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.
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.
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.
肿瘤微环境（TME）在许多癌症的肿瘤发生、进展和治疗反应中起着至关重要的作用。目前，TME在急性髓系白血病（AML）中的作用尚不清楚。本研究调查了AML患者免疫相关基因与预后之间的相关性。
整合素淋巴细胞功能相关抗原1（CD11A/CD18；ITGAL/ITGB2）被确定为显著影响AML患者预后的关键免疫相关基因。ITGB2的过表达表明AML患者预后不良（P=0.007）。风险模型表明，高风险评分导致AML患者预后不良（P=3.076e-08）。风险模型显示出预测AML患者预后的准确性，1年时曲线下面积（AUC）为0.816；3年时AUC为0.82；5年时AUC为0.875。此外，我们发现ITGB2对免疫细胞浸润AML TME有强大影响。免疫组织化学结果显示，AML患者的ITGB2蛋白表达明显高于正常样本。根据ITGB2风险评分将AML患者分为两组。药物敏感性测试结果表明，高风险组对阿糖胞苷、阿昔替尼、博舒替尼和多西他赛敏感，但对顺铂和硼替佐米耐药。
在本研究中，我们发现ITGB2可能能够作为评估AML患者预后和药物敏感性的生物标志物。
