Department of Hematology, West China Hospital, Sichuan University, Chengdu, China.
Department of Hematology, The Affiliated Hospital of Yunnan University, Kunming, China.
Hematol Oncol. 2022 Apr;40(2):172-180. doi: 10.1002/hon.2956. Epub 2021 Dec 17.
Exosomal microRNAs (miRNAs) are potential biomarkers for a variety of tumors, but have not yet been studied in diffuse large B-cell lymphoma (DLBCL). Here, we investigated the use of exosomal miRNAs in DLBCL diagnosis and prognosis. A total of 256 individuals, including 133 DLBCL patients, 94 healthy controls (HCs), and 29 non-DLBCL concurrent controls (CCs), were enrolled. Exosomal miRNAs were profiled in the screening stage using microarray analysis, and miRNA candidates were confirmed in training, testing, and external testing stages using qRT-PCR. Follow-up information on the DLBCL patients was collected, and miRNAs were used to develop diagnostic and prognostic models for these patients. Five exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-4476, miR-483-3p, and miR-451a) were differentially expressed between DLBCL patients and HCs with areas under the receiver operating characteristic curve (AUC) of 0.86, 0.90, and 0.86 for the training, testing, and external testing stages, respectively. Four exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-4476, and miR-451a) were differentially expressed between patients with DLBCL and CCs, with an AUC of 0.78. One miRNA (miR-451a) was significantly associated with both progression-free survival (PFS) and overall survival (OS) of DLBCL patients, R analysis indicated the combination of miR-451a with international prognostic index was a better predictor of PFS and OS for these patients. Our study suggests that subsets of circulating exosomal miRNAs can be useful noninvasive biomarkers for the diagnosis of DLBCL and that the use of circulating exosomal miRNAs improves the identification of patients with newly diagnosed DLBCL with poor outcomes.
细胞外体 microRNAs（miRNAs）是多种肿瘤的潜在生物标志物，但尚未在弥漫性大 B 细胞淋巴瘤（DLBCL）中进行研究。在这里，我们研究了细胞外体 miRNAs 在 DLBCL 诊断和预后中的应用。共纳入 256 人，包括 133 例 DLBCL 患者、94 例健康对照（HCs）和 29 例非 DLBCL 同期对照（CCs）。在筛选阶段，使用微阵列分析对细胞外体 miRNAs 进行了分析，在训练、测试和外部测试阶段使用 qRT-PCR 对 miRNA 候选物进行了验证。收集了 DLBCL 患者的随访信息，并使用这些 miRNA 为这些患者开发了诊断和预后模型。在训练、测试和外部测试阶段，miR-379-5p、miR-135a-3p、miR-4476、miR-483-3p 和 miR-451a 这 5 个细胞外体 miRNAs 在 DLBCL 患者与 HCs 之间的表达差异具有诊断价值，ROC 曲线下面积（AUC）分别为 0.86、0.90 和 0.86。miR-379-5p、miR-135a-3p、miR-4476 和 miR-451a 这 4 个细胞外体 miRNAs 在 DLBCL 患者与 CCs 之间的表达差异具有诊断价值，AUC 为 0.78。一个 miRNA（miR-451a）与 DLBCL 患者的无进展生存（PFS）和总生存（OS）均显著相关，R 分析表明，miR-451a 与国际预后指数（IPI）联合可更好地预测这些患者的 PFS 和 OS。本研究表明，循环细胞外体 miRNAs 的亚群可作为 DLBCL 诊断的有用非侵入性生物标志物，并且使用循环细胞外体 miRNAs 可提高对新诊断为预后不良的 DLBCL 患者的识别能力。
