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自噬相关基因根据染色体异常情况影响多发性骨髓瘤患者的生存。

Autophagy-related genes affect the survival of multiple myeloma patients depending on chromosomal abnormality.

作者信息

Ayna Duran Gizem, Benderli Cihan Yasemin

机构信息

Department of Biomedical Engineering, Faculty of Engineering, Izmir University of Economics, Balçova, İzmir 35330, Turkey.

Department of Radiation Oncology, Kayseri City Education and Research Hospital, Kocasinan, Kayseri 38080, Turkey.

出版信息

Asian Biomed (Res Rev News). 2023 Jun 16;16(5):249-264. doi: 10.2478/abm-2022-0028. eCollection 2022 Oct.

DOI:10.2478/abm-2022-0028
PMID:37551318
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10321186/
Abstract

BACKGROUND

Targeting autophagy at gene level may be promising in multiple myeloma (MM) treatment depending on chromosomal abnormality (ABN) status.

OBJECTIVES

We aimed to investigate the role of ABN on survival of MM patients and to identify prognosis related autophagy-related genes (ARGs) for patients with or without ABN.

METHODS

Gene intensity values of 222 ARG for 548 MM patients were obtained from the Affymetrix Human Genome U133 Plus 2.0 Array (GPL570) platform containing 54,675 probes (GSE24080). A dataset containing data from 1576 MM patients with 1q21 amplification (GSE4204, GSE4452, GSE4581, and GSE2658) was used for validation. Survival analysis of the patients was analyzed using univariate and multivariate Cox regression method with the help of R3.53 programming language and Kaplan-Meier graphics were created. The Gene Ontology enRIchmentanaLysis and visuaLizAtion (GOrilla) tool was used to define the related biological processes and pathways.

RESULTS

The overall survival (OS) and event-free survival (EFS) in all MM patients were strongly influenced by ABN. In the group of patients with ABN, 41 ARGs were found to be important in prognosis, whereas in the group of patients without ABN, 13 ARGs were found to be important in prognosis. , , , and ARGs were commonly significant in both groups and found to be survival triggering.

CONCLUSIONS

The classification of MM patients according to the absence or presence of ABN is important in the determination of survival status. Detection of survival related ARGs in patients with chromosomal anomalies may be a new therapeutic target in treatment.

摘要

背景

根据染色体异常(ABN)状态,在基因水平上靶向自噬可能在多发性骨髓瘤(MM)治疗中具有前景。

目的

我们旨在研究ABN对MM患者生存的作用,并确定有或无ABN患者的预后相关自噬相关基因(ARG)。

方法

从包含54,675个探针的Affymetrix人类基因组U133 Plus 2.0阵列(GPL570)平台获取548例MM患者的222个ARG的基因强度值(GSE24080)。使用包含1576例1q21扩增MM患者数据的数据集(GSE4204、GSE4452、GSE4581和GSE2658)进行验证。借助R3.53编程语言,使用单变量和多变量Cox回归方法对患者进行生存分析,并创建Kaplan-Meier图。使用基因本体富集分析和可视化(GOrilla)工具定义相关的生物学过程和途径。

结果

所有MM患者的总生存期(OS)和无事件生存期(EFS)均受到ABN的强烈影响。在有ABN的患者组中,发现41个ARG对预后很重要,而在无ABN的患者组中,发现13个ARG对预后很重要。 、 、 和 个ARG在两组中均普遍显著,并被发现具有生存触发作用。

结论

根据有无ABN对MM患者进行分类对确定生存状态很重要。检测染色体异常患者中与生存相关的ARG可能是治疗中的一个新治疗靶点。

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本文引用的文献

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Development of an autophagy-related gene expression signature for prognosis prediction in prostate cancer patients.建立一个自噬相关基因表达谱,用于预测前列腺癌患者的预后。
J Transl Med. 2020 Apr 7;18(1):160. doi: 10.1186/s12967-020-02323-x.
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A predicted risk score based on the expression of 16 autophagy-related genes for multiple myeloma survival.基于16个自噬相关基因表达的多发性骨髓瘤生存预测风险评分。
Oncol Lett. 2019 Nov;18(5):5310-5324. doi: 10.3892/ol.2019.10881. Epub 2019 Sep 19.
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