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通过随机森林和列线图鉴定 MNS1、FRZB、OGN、LUM、SERP1NA3 和 FCN3 为潜在的与免疫相关的缺血性心肌病关键基因。

Identification MNS1, FRZB, OGN, LUM, SERP1NA3 and FCN3 as the potential immune-related key genes involved in ischaemic cardiomyopathy by random forest and nomogram.

机构信息

Cardiology Department, Hunan Provincial People’s Hospital, Furong, Changsha 410000, Hunan, China.

Clinical Research Center for Heart Failure in Hunan Province, Furong, Changsha 410000, Hunan, China.

出版信息

Aging (Albany NY). 2023 Feb 27;15(5):1475-1495. doi: 10.18632/aging.204547.

DOI:10.18632/aging.204547
PMID:36863704
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10042686/
Abstract

The immune molecular mechanisms involved in ischaemic cardiomyopathy (ICM) have not been fully elucidated. The current study aimed to elucidate the immune cell infiltration pattern of the ICM and identify key immune-related genes that participate in the pathologic process of the ICM. The differentially expressed genes (DEGs) were identified from two datasets (GSE42955 combined with GSE57338) and the top 8 key DEGs related to ICM were screened using random forest and used to construct the nomogram model. Moreover, the "CIBERSORT" software package was used to determine the proportion of infiltrating immune cells in the ICM. A total of 39 DEGs (18 upregulated and 21 downregulated) were identified in the current study. Four upregulated DEGs, including , , , and and four downregulated DEGs, , and were identified by the random forest model. The nomogram constructed based on the above 8 key genes suggested a diagnostic value of up to 99% to distinguish the ICM from healthy participants. Meanwhile, most of the key DEGs presented prominent interactions with immune cell infiltrates. The RT-qPCR results suggested that the expression levels of , , , , and between the ICM and control groups were consistent with the bioinformatic analysis results. These results suggested that immune cell infiltration plays a critical role in the occurrence and progression of ICM. Several key immune-related genes, including the , , , , and genes, are expected to be reliable serum markers for the diagnosis of ICM and potential molecular targets for ICM immunotherapy.

摘要

缺血性心肌病 (ICM) 涉及的免疫分子机制尚未完全阐明。本研究旨在阐明 ICM 的免疫细胞浸润模式,并确定参与 ICM 病理过程的关键免疫相关基因。从两个数据集(GSE42955 与 GSE57338 相结合)中鉴定出差异表达基因(DEGs),并使用随机森林筛选与 ICM 相关的前 8 个关键 DEGs,用于构建列线图模型。此外,使用“CIBERSORT”软件包确定 ICM 中浸润免疫细胞的比例。本研究共鉴定出 39 个 DEGs(18 个上调和 21 个下调)。随机森林模型鉴定出 4 个上调的 DEGs,包括、、和,以及 4 个下调的 DEGs、、和。基于上述 8 个关键基因构建的列线图提示,其对 ICM 与健康参与者的鉴别诊断具有高达 99%的诊断价值。同时,大多数关键 DEGs 与免疫细胞浸润呈显著相互作用。RT-qPCR 结果表明,ICM 组和对照组之间的、、、、和的表达水平与生物信息学分析结果一致。这些结果表明,免疫细胞浸润在 ICM 的发生和进展中起关键作用。几个关键的免疫相关基因,包括、、、、和基因,有望成为 ICM 诊断的可靠血清标志物和 ICM 免疫治疗的潜在分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/45ab5f1ac67c/aging-15-204547-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/77d5b897d758/aging-15-204547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/64bd23edafb3/aging-15-204547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/6e0aedc3a6f3/aging-15-204547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/23c71ce0faeb/aging-15-204547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/4a31023e1fe7/aging-15-204547-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/4b54a09d02da/aging-15-204547-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/eb17c09c6eec/aging-15-204547-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/6f5ef5a80834/aging-15-204547-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/45ab5f1ac67c/aging-15-204547-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/77d5b897d758/aging-15-204547-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/64bd23edafb3/aging-15-204547-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/6e0aedc3a6f3/aging-15-204547-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/23c71ce0faeb/aging-15-204547-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/4a31023e1fe7/aging-15-204547-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/4b54a09d02da/aging-15-204547-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/eb17c09c6eec/aging-15-204547-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/6f5ef5a80834/aging-15-204547-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d09e/10042686/45ab5f1ac67c/aging-15-204547-g009.jpg

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