Liang Chaofeng, Zhao Yujie, Chen Cunte, Huang Shuxin, Deng Tairan, Zeng Xiangbo, Tan Jiaxiong, Zha Xianfeng, Chen Shaohua, Li Yangqiu
Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
Front Oncol. 2021 Oct 8;11:740642. doi: 10.3389/fonc.2021.740642. eCollection 2021.
Thymocyte selection-associated HMG box (TOX) is a transcription factor that belongs to the high mobility group box (HMG-box) superfamily, which includes four subfamily members: TOX, TOX2, TOX3, and TOX4. TOX is related to the formation of multiple malignancies and contributes to CD8+ T cell exhaustion in solid tumors. However, little is known about the role of TOX genes in hematological malignancies. In this study, we explored the prognostic value of TOX genes from 40 patients with acute myeloid leukemia (AML) by quantitative real-time PCR (qRT-PCR) in a training cohort and validated the results using transcriptome data from 167 AML patients from the Cancer Genome Atlas (TCGA) database. In the training cohort, higher expression of and was detected in the AML samples, whereas lower expression was found. Moreover, both the training and validation results indicated that higher , , and expression of AML patients (3-year OS: 0% 37%, = 0.036; 3-year OS: 4% 61%, < 0.001; 3-year OS: 0% 32%, = 0.010) and the AML patients with highly co-expressed , , genes (3-year OS: 0% 25% 75%, = 0.001) were associated with poor overall survival (OS). Interestingly, was positively correlated with , , , and (r = 0.43, = 0.006; r = 0.43, = 0.006; r = 0.56, < 0.001; r = 0.54, < 0.001). In conclusion, higher expression of TOX genes was associated with poor OS for AML patients, which was related to the up-regulation of immune checkpoint genes. These data might provide novel predictors for AML outcome and direction for further investigation of the possibility of using TOX genes in novel targeted therapies for AML.
胸腺细胞选择相关HMG盒蛋白（TOX）是一种转录因子，属于高迁移率族盒（HMG盒）超家族，该超家族包括四个亚家族成员：TOX、TOX2、TOX3和TOX4。TOX与多种恶性肿瘤的形成有关，并导致实体瘤中CD8 + T细胞耗竭。然而，关于TOX基因在血液系统恶性肿瘤中的作用知之甚少。在本研究中，我们通过定量实时PCR（qRT-PCR）在一个训练队列中探索了40例急性髓系白血病（AML）患者中TOX基因的预后价值，并使用来自癌症基因组图谱（TCGA）数据库的167例AML患者的转录组数据验证了结果。在训练队列中，AML样本中检测到TOX2和TOX4表达较高，而TOX3表达较低。此外，训练和验证结果均表明，AML患者中TOX2、TOX3和TOX4表达较高（3年总生存率：0%对37%，P = 0.036；3年总生存率：4%对61%，P < 0.001；3年总生存率：0%对32%，P = 0.010）以及TOX2、TOX3、TOX4基因高共表达的AML患者（3年总生存率：0%对25%对75%，P = 0.001）与较差的总生存期（OS）相关。有趣的是，TOX2与TOX、TOX3、TOX4呈正相关（r = 0.43，P = 0.006；r = 0.43，P = 0.006；r = 0.56，P < 0.001；r = 0.54，P < 0.001）。总之，TOX基因高表达与AML患者较差的OS相关，这与免疫检查点基因的上调有关。这些数据可能为AML的预后提供新的预测指标，并为进一步研究TOX基因在AML新型靶向治疗中的可能性提供方向。
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