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骨肿瘤中细胞焦亡相关基因及 hub 基因 TP63 ceRNA 轴的分析。

The analysis of the pyroptosis-related genes and hub gene TP63 ceRNA axis in osteosarcoma.

机构信息

School of Graduates, Dalian Medical University, Dalian, China.

Department of Orthopedics, Dalian Municipal Central Hospital, Dalian City, China.

出版信息

Front Immunol. 2022 Nov 1;13:974916. doi: 10.3389/fimmu.2022.974916. eCollection 2022.

DOI:10.3389/fimmu.2022.974916
PMID:36389801
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9664215/
Abstract

Pyroptosis is a type of programmed cell death that is associated with tumor development, prognosis, and therapeutic response. The significance of pyroptosis-related genes (PRGs) in the tumor microenvironment (TME) remains unclear. We examined the expression patterns of PRGs in 141 OS samples from two different datasets and characterized the genetic and transcriptional changes in PRGs. Based on these PRGs, all OS samples could be classified into two clusters. We discovered that multilayer PRG changes were linked to clinicopathological traits, prognosis, and TME characteristics in two separate genetic subtypes. The PRG score was then developed for predicting overall survival, and its predictive efficacy in OS patients was tested. As a result, we developed a very precise nomogram to improve the PRG-predictive model in clinical application. Furthermore, a competing endogenous RNA (ceRNA) network was built to find a LAMTOR5-AS1/hsa-miR-23a-3p/TP63 regulatory axis. Through experimental verification, it was found that the pyroptosis gene TP63 plays an important role in the regulation of osteosarcoma pyroptosis. The possible functions of PRGs in the TME, clinicopathological characteristics, and prognosis were established in our investigation of PRGs in OS. These findings may aid in our understanding of PRGs in OS as well as provide a novel way for prognostic evaluation and the creation of more effective immunotherapy treatments.

摘要

细胞焦亡是一种与肿瘤发生、发展、预后及治疗反应相关的程序性细胞死亡方式。焦亡相关基因（PRGs）在肿瘤微环境（TME）中的意义尚不清楚。我们检测了来自两个不同数据集的 141 例骨肉瘤样本中 PRGs 的表达模式，并对 PRGs 的遗传和转录变化进行了特征分析。基于这些 PRGs，所有骨肉瘤样本可分为两个聚类。我们发现，两层 PRG 变化与两个独立遗传亚型中的临床病理特征、预后和 TME 特征有关。随后，我们开发了 PRG 评分来预测总生存期，并在骨肉瘤患者中进行了预测效能的检验。结果，我们开发了一个非常精确的列线图，以提高 PRG 预测模型在临床应用中的准确性。此外，构建了一个竞争性内源性 RNA（ceRNA）网络，发现了 LAMTOR5-AS1/hsa-miR-23a-3p/TP63 调控轴。通过实验验证，发现焦亡基因 TP63 在调控骨肉瘤焦亡中起重要作用。在对骨肉瘤中 PRGs 的研究中，我们确定了 PRGs 在 TME、临床病理特征和预后中的可能功能。这些发现可能有助于我们理解骨肉瘤中 PRGs 的作用，并为预后评估和创建更有效的免疫治疗提供新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/9296d5013ad1/fimmu-13-974916-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/736ffe624ba1/fimmu-13-974916-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/7aae127fac49/fimmu-13-974916-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/9296d5013ad1/fimmu-13-974916-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/736ffe624ba1/fimmu-13-974916-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/0adef44ac32d/fimmu-13-974916-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a61d/9664215/9296d5013ad1/fimmu-13-974916-g007.jpg

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