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A novel NET-related gene signature for predicting DLBCL prognosis

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机构: [1]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China. [2]Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu 610052, Sichuan, China. [3]Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu 610052, Sichuan, China. [4]School of Public Health, Anhui Medical University, Hefei 230032, China. [5]Department of Cardiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China. [6]Stomatology Center, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310000, China. [7]Department of Blood Transfusion, the Third People’s Hospital of Chengdu, Affiliated Hospital of Southwest Jiaotong University, 82 Qinglong Street, Qingyang District, Chengdu 610031, Sichuan, China.
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关键词: Diffuse large B-cell lymphoma Neutrophil extracellular traps Prognostic model Tumor microenvironment Prognostic biomarker

摘要:
Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy. Neutrophil extracellular traps (NETs) are pathogen-trapping structures in the tumor microenvironment that affect DLBCL progression. However, the predictive function of NET-related genes (NRGs) in DLBCL has received little attention. This study aimed to investigate the interaction between NRGs and the prognosis of DLBCL as well as their possible association with the immunological microenvironment.The gene expression and clinical data of patients with DLBCL were downloaded from the Gene Expression Omnibus database. We identified 148 NRGs through the manual collection of literature. GSE10846 (n = 400, GPL570) was used as the training dataset and divided into training and testing sets in a 7:3 ratio. Univariate Cox regression analysis was used to identify overall survival (OS)-related NETs, and the least absolute shrinkage and selection operator was used to evaluate the predictive efficacy of the NRGs. Kaplan-Meier plots were used to visualize survival functions. Receiver operating characteristic (ROC) curves were used to assess the prognostic predictive ability of NRG-based features. A nomogram containing the clinical information and prognostic scores of the patients was constructed using multivariate logistic regression and Cox proportional risk regression models.We identified 36 NRGs that significantly affected patient overall survival (OS). Eight NRGs (PARVB, LYZ, PPARGC1A, HIF1A, SPP1, CDH1, S100A9, and CXCL2) were found to have excellent predictive potential for patient survival. For the 1-, 3-, and 5-year survival rates, the obtained areas under the receiver operating characteristic curve values were 0.8, 0.82, and 0.79, respectively. In the training set, patients in the high NRG risk group presented a poorer prognosis (p < 0.0001), which was validated using two external datasets (GSE11318 and GSE34171). The calibration curves of the nomogram showed that it had excellent predictive ability. Moreover, in vitro quantitative real-time PCR (qPCR) results showed that the mRNA expression levels of CXCL2, LYZ, and PARVB were significantly higher in the DLBCL group.We developed a genetic risk model based on NRGs to predict the prognosis of patients with DLBCL, which may assist in the selection of treatment drugs for these patients.© 2023. BioMed Central Ltd., part of Springer Nature.

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验
第一作者:
第一作者机构: [1]Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100 Haining Road, Shanghai 200080, China.
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通讯作者:
通讯机构: [2]Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu 610052, Sichuan, China. [3]Key Laboratory of Transfusion Adverse Reactions, Chinese Academy of Medical Sciences, 26 Huacai Rd, Longtan Industry Zone, Chenghua District, Chengdu 610052, Sichuan, China. [4]School of Public Health, Anhui Medical University, Hefei 230032, China.
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