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谷氨酰胺代谢相关长链非编码RNA(lncRNA)作为多发性骨髓瘤患者预后生物标志物的潜力。

The potential of glutamine metabolism-related long non-coding RNAs (lncRNAs) as prognostic biomarkers in multiple myeloma patients.

作者信息

Zhong Yun, Xu Shenghua, Liu Zhe

机构信息

Department of Lymphohematology and Oncology, Jiangxi Cancer Hospital, Nanchang, China.

Department of Orthopedics, Jiangxi Cancer Hospital, Nanchang, China.

出版信息

Ann Transl Med. 2022 Dec;10(24):1362. doi: 10.21037/atm-22-6190.

Abstract

BACKGROUND

Glutamine (Gln) metabolism has been confirmed as an important fuel in cancer metabolism. This study aimed to uncover potential links of Gln with long non-coding RNAs (lncRNAs) and the prognostic value of Gln-associated lncRNAs in multiple myeloma (MM) patients.

METHODS

The RNA-seq expression profile and corresponding clinical data of gastric cancer obtained from Gene Expression Omnibus (GEO) database. Unsupervised consensus clustering was used to cluster MM samples based on Gln-associated lncRNAs. The overall survival (OS), biological pathways, and immune microenvironment were compared in different subtypes. Differential analysis was utilized to identify differentially expressed lncRNAs (DElncRNAs) in different subtypes. A risk model was constructed based on DElncRNAs by using Cox regression, least absolute shrinkage and selection operator (LASSO), and the stepAIC algorithm.

RESULTS

We screened 50 Gln-associated lncRNAs and identified 3 molecular subtypes (clust1, clust2, and clust3) based on lncRNA expression profiles. Clust3 subtype showed the worst prognosis and highest enrichment of Gln metabolism pathway. Angiogenesis, epithelial-mesenchymal transition (EMT), and cell cycle-related pathways were relatively activated in clust3. Then, we identified 11 prognostic DElncRNAs for constructing the risk model. The MM samples were divided into high- and low-risk groups with distinct prognosis according to the risk score. The risk score was significantly associated with cell cycle and infiltration of many immune cells.

CONCLUSIONS

This study characterized the role of Gln-associated lncRNAs in Gln metabolism contributing for tumor-related pathways and immune microenvironment in MM patients. The 11 lncRNAs in the risk model may serve as potential targets for exploring the mechanism of Gln metabolism or serve as potential biomarkers for MM prognosis.

摘要

背景

谷氨酰胺(Gln)代谢已被确认为癌症代谢中的一种重要燃料。本研究旨在揭示Gln与长链非编码RNA(lncRNAs)之间的潜在联系以及Gln相关lncRNAs在多发性骨髓瘤(MM)患者中的预后价值。

方法

从基因表达综合数据库(GEO)获取胃癌的RNA测序表达谱及相应临床数据。基于Gln相关lncRNAs,采用无监督一致性聚类对MM样本进行聚类。比较不同亚型的总生存期(OS)、生物学通路和免疫微环境。利用差异分析鉴定不同亚型中差异表达的lncRNAs(DElncRNAs)。通过Cox回归、最小绝对收缩和选择算子(LASSO)以及逐步AIC算法,基于DElncRNAs构建风险模型。

结果

我们筛选出50个Gln相关lncRNAs,并基于lncRNA表达谱鉴定出3种分子亚型(clust1、clust2和clust3)。Clust3亚型预后最差,Gln代谢通路富集程度最高。血管生成、上皮-间质转化(EMT)和细胞周期相关通路在clust3中相对激活。然后,我们鉴定出11个用于构建风险模型的预后DElncRNAs。根据风险评分,MM样本被分为预后不同的高风险组和低风险组。风险评分与细胞周期及多种免疫细胞浸润显著相关。

结论

本研究阐述了Gln相关lncRNAs在Gln代谢中的作用,其对MM患者肿瘤相关通路和免疫微环境有影响。风险模型中的11个lncRNAs可能作为探索Gln代谢机制的潜在靶点,或作为MM预后的潜在生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46b6/9843343/e5b9a5d67be5/atm-10-24-1362-f1.jpg

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