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转录组和单细胞分析揭示骨肉瘤肿瘤微环境中与二硫键介导的铁死亡相关的修饰模式及预后情况。

Transcriptome and single-cell analysis reveal disulfidptosis-related modification patterns of tumor microenvironment and prognosis in osteosarcoma.

作者信息

Wang Linbang, Liu Yu, Tai Jiaojiao, Dou Xinyu, Yang Hongjuan, Li Qiaochu, Liu Jingkun, Yan Ziqiang, Liu Xiaoguang

机构信息

Department of Orthopaedics, Peking University Third Hospital, Beijing, People's Republic of China.

Department of Orthopedics, Honghui Hospital, Xi'an Jiaotong University, No. 555, Youyi Road, Beilin District, Xi'an, 710054, Shaanxi, People's Republic of China.

出版信息

Sci Rep. 2024 Apr 22;14(1):9186. doi: 10.1038/s41598-024-59243-9.

DOI:10.1038/s41598-024-59243-9
PMID:38649690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11035678/
Abstract

Osteosarcoma (OS) is the most common malignant bone tumor with high pathological heterogeneity. Our study aimed to investigate disulfidptosis-related modification patterns in OS and their relationship with survival outcomes in patients with OS. We analyzed the single-cell-level expression profiles of disulfidptosis-related genes (DSRGs) in both OS microenvironment and OS subclusters, and HMGB1 was found to be crucial for intercellular regulation of OS disulfidptosis. Next, we explored the molecular clusters of OS based on DSRGs and related immune cell infiltration using transcriptome data. Subsequently, the hub genes of disulfidptosis in OS were screened by applying multiple machine models. In vitro and patient experiments validated our results. Three main disulfidptosis-related molecular clusters were defined in OS, and immune infiltration analysis suggested high immune heterogeneity between distinct clusters. The in vitro experiment confirmed decreased cell viability of OS after ACTB silencing and higher expression of ACTB in patients with lower immune scores. Our study systematically revealed the underlying relationship between disulfidptosis and OS at the single-cell level, identified disulfidptosis-related subtypes, and revealed the potential role of ACTB expression in OS disulfidptosis.

摘要

骨肉瘤（OS）是最常见的恶性骨肿瘤，具有高度的病理异质性。我们的研究旨在探讨骨肉瘤中与二硫键连接性坏死相关的修饰模式及其与骨肉瘤患者生存结果的关系。我们分析了骨肉瘤微环境和骨肉瘤亚群中二硫键连接性坏死相关基因（DSRGs）的单细胞水平表达谱，发现高迁移率族蛋白B1（HMGB1）对骨肉瘤二硫键连接性坏死的细胞间调节至关重要。接下来，我们利用转录组数据，基于DSRGs和相关免疫细胞浸润情况，探索了骨肉瘤的分子簇。随后，通过应用多种机器学习模型，筛选出了骨肉瘤中二硫键连接性坏死的关键基因。体外实验和患者实验验证了我们的结果。在骨肉瘤中定义了三个主要的与二硫键连接性坏死相关的分子簇，免疫浸润分析表明不同簇之间存在高度的免疫异质性。体外实验证实，肌动蛋白（ACTB）沉默后骨肉瘤细胞活力下降，且免疫评分较低的患者中ACTB表达较高。我们的研究系统地揭示了二硫键连接性坏死与骨肉瘤在单细胞水平上的潜在关系，确定了与二硫键连接性坏死相关的亚型，并揭示了ACTB表达在骨肉瘤二硫键连接性坏死中的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/a4fca1476e25/41598_2024_59243_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/7d12ea0a1851/41598_2024_59243_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/a4fca1476e25/41598_2024_59243_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/7d12ea0a1851/41598_2024_59243_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/58c3de4cd66c/41598_2024_59243_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/08f9a5691151/41598_2024_59243_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/8fc23c2f7830/41598_2024_59243_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/ca916d28720a/41598_2024_59243_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20e8/11035678/a4fca1476e25/41598_2024_59243_Fig8_HTML.jpg

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