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鉴定弥漫性大 B 细胞淋巴瘤基于个体化 RNA 结合蛋白的预后特征。

Identification of an individualized RNA binding protein-based prognostic signature for diffuse large B-cell lymphoma.

机构信息

Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, China.

School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China.

出版信息

Cancer Med. 2021 Apr;10(8):2703-2713. doi: 10.1002/cam4.3859. Epub 2021 Mar 21.

Abstract

RNA binding proteins (RBPs) are increasingly appreciated as being essential for normal hematopoiesis and have a critical role in the progression of hematological malignancies. However, their functional consequences and clinical significance in diffuse large B-cell lymphoma (DLBCL) remain unknown. Here, we conducted a systematic analysis to identify RBP-related genes affecting DLBCL prognosis based on the Gene Expression Omnibus database. By univariate and multivariate Cox proportional hazards regression (CPHR) methods, six RBPs-related genes (CMSS1, MAEL, THOC5, PSIP1, SNIP1, and ZCCHC7) were identified closely related to the overall survival (OS) of DLBCL patients. The RBPs signature could efficiently distinguished low-risk from high-risk patients and could serve as an independent and reliable factor for predicting OS. Moreover, Gene Set Enrichment Analysis revealed 17 significantly enriched pathways between high- versus low-risk group, including the regulation of autophagy, chronic myeloid leukemia, NOTCH signaling pathway, and B cell receptor signaling pathway. Then we developed an RBP-based nomogram combining other clinical risk factors. The receiver operating characteristic curve analysis demonstrated high prognostic predictive efficiency of this model with the area under the curve values were 0.820 and 0.780, respectively, in the primary set and entire set. In summary, our RBP-based model could be a novel prognostic predictor and had the potential for developing treatment targets for DLBCL.

摘要

RNA 结合蛋白 (RBPs) 在正常造血中被认为是必不可少的,并且在血液恶性肿瘤的进展中起着关键作用。然而,它们在弥漫性大 B 细胞淋巴瘤 (DLBCL) 中的功能后果和临床意义仍不清楚。在这里,我们基于基因表达综合数据库进行了系统分析,以确定影响 DLBCL 预后的 RBP 相关基因。通过单变量和多变量 Cox 比例风险回归 (CPHR) 方法,确定了六个与 DLBCL 患者总生存 (OS) 密切相关的 RBP 相关基因 (CMSS1、MAEL、THOC5、PSIP1、SNIP1 和 ZCCHC7)。RBP 特征可以有效地将低风险和高风险患者区分开来,并且可以作为预测 OS 的独立和可靠因素。此外,基因集富集分析揭示了高风险组与低风险组之间存在 17 个显著富集的通路,包括自噬调控、慢性髓性白血病、NOTCH 信号通路和 B 细胞受体信号通路。然后,我们开发了一种基于 RBP 的列线图,结合其他临床危险因素。受试者工作特征曲线分析表明,该模型具有较高的预后预测效率,其曲线下面积值分别为 0.820 和 0.780,在原发性组和全组中。总之,我们的基于 RBP 的模型可以作为一种新的预后预测指标,并有可能为 DLBCL 开发治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f285/8026940/b07ef20c8806/CAM4-10-2703-g008.jpg

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