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弥漫性大B细胞淋巴瘤中微管相关生物标志物的鉴定及预后预测

Identification of microtubule-associated biomarkers in diffuse large B-cell lymphoma and prognosis prediction.

作者信息

Wu Wenqi, Liu Su, Tian Linyan, Li Cheng, Jiang Yanan, Wang Jinhuan, Lv Yangyang, Guo Jing, Xing Donghui, Zhai Yixin, Sun Huimeng, Li Yuhang, Zhang Luying, He Xiang, Luo Kaiping, Zhan Hongjie, Zhao Zhigang

机构信息

Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Department of Medical Oncology, Tianjin First Central Hospital, School of Medicine. Nankai University, Tianjin, China.

出版信息

Front Genet. 2023 Jan 24;13:1092678. doi: 10.3389/fgene.2022.1092678. eCollection 2022.

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with a complicated prognosis. Even though various prognostic evaluations have been applied currently, they usually only use the clinical factors that overlook the molecular underlying DLBCL progression. Therefore, more accurate prognostic assessment needs further exploration. In the present study, we constructed a novel prognostic model based on microtubule associated genes (MAGs). A total of 33 normal controls and 1360 DLBCL samples containing gene-expression from the Gene Expression Omnibus (GEO) database were included. Subsequently, the univariate Cox, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis were used to select the best prognosis related genes into the MAGs model. To validate the model, Kaplan-Meier curve, and nomogram were analyzed. A risk score model based on fourteen candidate MAGs () was established. The K-M curve presented that the high-risk patients had a significantly inferior overall survival (OS) time compared to low-risk patients in training and validation datasets. Furthermore, knocking-out , a key gene belonging to the MAGs model, inhibited cell proliferation noticeably. The novel MAGs prognostic model has a well predictive capability, which may as a supplement for the current assessments. Furthermore, candidate TMEM63A gene has therapeutic target potentially in DLBCL.

摘要

弥漫性大B细胞淋巴瘤(DLBCL)是一种具有复杂预后的基因异质性疾病。尽管目前已应用了各种预后评估方法,但它们通常仅使用临床因素,而忽略了DLBCL进展的分子基础。因此,需要进一步探索更准确的预后评估方法。在本研究中,我们构建了一种基于微管相关基因(MAGs)的新型预后模型。共纳入了33例正常对照和1360例来自基因表达综合数据库(GEO)的包含基因表达的DLBCL样本。随后,使用单变量Cox分析、最小绝对收缩和选择算子(LASSO)以及多变量Cox回归分析,将最佳预后相关基因纳入MAGs模型。为验证该模型,分析了Kaplan-Meier曲线和列线图。建立了基于14个候选MAGs的风险评分模型。K-M曲线显示,在训练集和验证集中,高危患者的总生存期(OS)明显低于低危患者。此外,敲除属于MAGs模型的关键基因,显著抑制了细胞增殖。新型MAGs预后模型具有良好的预测能力,可作为当前评估的补充。此外,候选基因TMEM63A在DLBCL中可能具有治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ccb7/9902697/badb5c7da496/fgene-13-1092678-g001.jpg

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