Yu Zhengyu, Qiu Bingquan, Li Linfeng, Xu Jing, Zhou Hui, Niu Ting
Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Front Oncol. 2022 Aug 30;12:992387. doi: 10.3389/fonc.2022.992387. eCollection 2022.
Multiple myeloma (MM), a hematologic malignancy, is characterized by malignant plasma cells clonal proliferation. Many evidences indicated the indirect interaction between hypoxic environment and immune state in MM tumorigenesis, but the underlying mechanism remains unclear. MM-related datasets were downloaded from the Gene Expression Omnibus (GEO) database. The R packages were applied for screening protective differentially expressed genes (DEGs) and risk DEGs. The signature was constructed based the most prognostic gene signature in the training and assessed in the validation cohorts. The immune cell infiltration, the expression of the HLA family and immune checkpoint genes inside the low- and high-risk groups were compared to determine the differences in immune infiltration and immunotherapy responses. Moreover, the expression of HLA families and immune checkpoints inside the low- and high-risk groups was markedly disordered. The results indicated hypoxia- and immune-related genes, including , , , , , , , and , were identified and used to construct a prognostic signature. Role of DDIT4 in multiple myeloma was confirmed and . DDIT4 knockdown inhibited MM cell viability, migration and invasion potential as well as promoted myeloma cells apoptosis under hypoxia. Taken together, our study may contribute to the treatment and prognosis prediction of MM.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，其特征为恶性浆细胞的克隆性增殖。许多证据表明，缺氧环境与MM肿瘤发生过程中的免疫状态之间存在间接相互作用，但其潜在机制仍不清楚。从基因表达综合数据库（GEO）下载了MM相关数据集。使用R软件包筛选保护性差异表达基因（DEG）和风险DEG。基于训练中预后最佳的基因特征构建特征，并在验证队列中进行评估。比较低风险组和高风险组内的免疫细胞浸润、HLA家族和免疫检查点基因的表达，以确定免疫浸润和免疫治疗反应的差异。此外，低风险组和高风险组内HLA家族和免疫检查点的表达明显紊乱。结果表明，已鉴定出包括、、、、、、和在内的缺氧和免疫相关基因，并用于构建预后特征。DDIT4在多发性骨髓瘤中的作用得到了和的证实。DDIT4基因敲低可抑制MM细胞活力、迁移和侵袭潜能，并在缺氧条件下促进骨髓瘤细胞凋亡。综上所述，我们的研究可能有助于MM的治疗和预后预测。
