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基于肿瘤微环境免疫相关 lncRNAs 的骨肉瘤治疗新治疗靶点的发现。

Discovery of New Therapeutic Targets for Osteosarcoma Treatment Based on Immune-Related lncRNAs in the Tumor Microenvironment.

机构信息

Department of Joint Surgery and Sports Medicine, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.

Department of Stomatology, Zhongshan Hospital, Xiamen University, Xiamen 361004, China.

出版信息

Biomed Res Int. 2022 Apr 26;2022:3113857. doi: 10.1155/2022/3113857. eCollection 2022.

DOI:10.1155/2022/3113857
PMID:35528175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9073548/
Abstract

BACKGROUND: Long noncoding RNAs (lncRNAs) play an important role in osteosarcoma development, but their role in the tumor microenvironment (TME) is not fully understood. This study associated lncRNAs with immune-related genes and explored the mechanism of lncRNAs in osteosarcoma progression. METHODS: Unsupervised consensus clustering was applied to construct immune subtypes based on immune-related lncRNAs identified by Pearson's correlation analysis. A series of functional analysis was performed to reveal the links among lncRNAs, immune subtypes, TME, and osteosarcoma prognosis. RESULTS: We identified two immune subtypes C1 and C2 showing distinct overall survival. ECM-receptor interaction pathway was more activated in C2 subtype, while immune response pathways were more enriched in C2 subtype. Differential TME and response to chemotherapeutic drugs were observed between the two subtypes. Four metagenes of costimulation, cytolytic activity (CYT), immune score, and STAT1 were differentially enriched in the two subtypes. Based on 26-paired lncRNAs, we constructed a 4-paired lncRNA prognostic signature for predicting prognosis of osteosarcoma prognosis. CONCLUSIONS: This study focused on immune-related lncRNAs and TME, showing the possible role and mechanisms of lncRNAs in tumor growth and metastasis. ECM may be the new therapeutic target for treating osteosarcoma, and 26-paired lncRNAs could serve as a basis for further studying the mechanisms of CYT and STAT1 in immune response, cancer cell proliferation, and migration. The two subtypes and prognostic signature could promote the design of personalized osteosarcoma treatment.

摘要

背景：长链非编码 RNA（lncRNA）在骨肉瘤发展中发挥着重要作用，但它们在肿瘤微环境（TME）中的作用尚不完全清楚。本研究将 lncRNA 与免疫相关基因相关联，并探讨了 lncRNA 在骨肉瘤进展中的作用机制。

方法：应用无监督一致性聚类方法，根据 Pearson 相关分析鉴定的免疫相关 lncRNA 构建免疫亚型。进行一系列功能分析，以揭示 lncRNA、免疫亚型、TME 和骨肉瘤预后之间的联系。

结果：我们鉴定出两种具有不同总体生存率的免疫亚型 C1 和 C2。C2 亚型中 ECM-受体相互作用途径更为活跃，而 C2 亚型中免疫反应途径更为丰富。观察到两种亚型之间存在不同的 TME 和对化疗药物的反应。在两种亚型中，共刺激、细胞毒性（CYT）、免疫评分和 STAT1 的四个代谢基因差异丰富。基于 26 对 lncRNA，我们构建了一个 4 对 lncRNA 预后签名，用于预测骨肉瘤预后。

结论：本研究重点关注免疫相关 lncRNA 和 TME，显示 lncRNA 在肿瘤生长和转移中的可能作用和机制。ECM 可能成为治疗骨肉瘤的新治疗靶点，26 对 lncRNA 可作为进一步研究 CYT 和 STAT1 在免疫反应、癌细胞增殖和迁移中的机制的基础。两种亚型和预后签名可以促进骨肉瘤个体化治疗的设计。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/3f51d2a1244f/BMRI2022-3113857.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/5d91b5a465f1/BMRI2022-3113857.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/2db14ea9c9f6/BMRI2022-3113857.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/5d91b5a465f1/BMRI2022-3113857.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/07f9b1cfed4e/BMRI2022-3113857.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/1453e3e8e9be/BMRI2022-3113857.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/c550d6a7895a/BMRI2022-3113857.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/2db14ea9c9f6/BMRI2022-3113857.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/a478095ffa1c/BMRI2022-3113857.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/4f7df45d5c32/BMRI2022-3113857.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b75f/9073548/3f51d2a1244f/BMRI2022-3113857.010.jpg

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引用本文的文献

[1]
Retracted: Discovery of New Therapeutic Targets for Osteosarcoma Treatment Based on Immune-Related lncRNAs in the Tumor Microenvironment.

Biomed Res Int. 2024-3-20

本文引用的文献

[1]
Cytolytic activity score as a biomarker for antitumor immunity and clinical outcome in patients with gastric cancer.

Cancer Med. 2021-5

[2]
Exosomal Long Non-coding RNAs: Emerging Players in the Tumor Microenvironment.

Mol Ther Nucleic Acids. 2020-10-4

[3]
The lncRNA NEAT1 promotes the epithelial-mesenchymal transition and metastasis of osteosarcoma cells by sponging miR-483 to upregulate STAT3 expression.

Cancer Cell Int. 2021-2-5

[4]
LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis.

J Exp Clin Cancer Res. 2020-9-5

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Immune Cytolytic Activity as an Indicator of Immune Checkpoint Inhibitors Treatment for Prostate Cancer.

Front Bioeng Biotechnol. 2020-8-6

[6]
Identification of Immune-Related Prognostic Genes and LncRNAs Biomarkers Associated With Osteosarcoma Microenvironment.

Front Oncol. 2020-7-24

[7]
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Cancers (Basel). 2020-5-13

[8]
STAT1-induced upregulation of lncRNA LINC01123 predicts poor prognosis and promotes the progression of endometrial cancer through miR-516b/KIF4A.

Cell Cycle. 2020-6

[9]
LncRNA LINC00588 Suppresses the Progression of Osteosarcoma by Acting as a ceRNA for miRNA-1972.

Front Pharmacol. 2020-3-24

[10]
Immuno-genomic landscape of osteosarcoma.

Nat Commun. 2020-2-21

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