Screening and identification Hub genes associated with immune cell infiltration and critical biomarkers in osteosarcoma

IF 2.3 3区生物学 Q3 BIOCHEMICAL RESEARCH METHODS

Molecular and Cellular Probes Pub Date : 2025-05-13 DOI:10.1016/j.mcp.2025.102031

Xin Song , Sihao Chen , Junning Cheng , Haiyu Li , Ruixin Wu , Min Yan , Min Wang , Jie Li , Aishun Jin , Wang Wang

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引用次数: 0

Abstract

Purpose

Osteosarcoma (OS) exhibits limited immune cell infiltration that directly contributes to poor prognosis. This study sought to screen and identify pivotal biomarkers of OS immune infiltration and early diagnosis of OS.

Methods

The immune cell infiltration profiles with transcriptome sequencing data from 88 OS samples were explored with CIBERSORT algorithm. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Protein-protein interaction (PPI) network analyses were applied to identify hub genes, with the expressions confirmed by dual immunofluorescence in 50 OS samples. The new biomarker gene HTRA1 were examined by immunohistochemistry and validated by the Immune score and immune gene expression profile analyses. The impact of HTRA1 on OS prognosis was verified by Least absolute shrinkage and selection operator (LASSO) regression analysis. The biological effect of HTRA1 was characterized in MG63 cells.

Result

CD8⁺ T cells, activated memory CD4⁺ T cells and plasma cells were positively correlated with the prognosis of OS. Hub genes CCL5, CXCL9, CXCL13, and HTRA1, exhibited positive correlation with the infiltration of both CD8⁺ T cells and CD4⁺ T cells. HTRA1 expression was reduced in osteosarcoma tissues, which was positively correlated with immune scores and the expressions of immune-related genes. High levels of HTRA1 were associated with favorable OS prognosis, and could negatively impacted MG63 malignant characteristics.

Conclusion

CCL5, CXCL9, CXCL13, and HTRA1 were OS hub genes positively correlate with CD8⁺ T cell and CD4⁺ T cell infiltrations. HTRA1 can serve as an underlying biomarker for the prognosis and immunotherapy of OS.

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筛选和鉴定骨肉瘤中与免疫细胞浸润相关的中枢基因和关键生物标志物。

目的：骨肉瘤（OS）表现出有限的免疫细胞浸润，直接导致预后不良。本研究旨在筛选和鉴定OS免疫浸润和OS早期诊断的关键生物标志物。方法：采用CIBERSORT算法对88例OS样本的免疫细胞浸润谱进行转录组测序分析。应用基因本体（GO）、京都基因与基因组百科全书（KEGG）和蛋白-蛋白相互作用（PPI）网络分析方法鉴定中心基因，并通过双免疫荧光法对50份OS样本的表达进行确认。通过免疫组织化学检测新的生物标志物基因HTRA1，并通过免疫评分和免疫基因表达谱分析进行验证。采用最小绝对收缩和选择算子（LASSO）回归分析验证HTRA1对OS预后的影响。在MG63细胞中表征了HTRA1的生物学效应。结果：CD8+ T细胞、活化记忆CD4+ T细胞、浆细胞与OS预后呈正相关。枢纽基因CCL5、CXCL9、CXCL13和HTRA1与CD8+ T细胞和CD4+ T细胞浸润均呈正相关。骨肉瘤组织中HTRA1表达降低，与免疫评分及免疫相关基因表达呈正相关。高水平的HTRA1与良好的OS预后相关，并可能对MG63的恶性特征产生负面影响。结论：CCL5、CXCL9、CXCL13和HTRA1是OS中心基因，与CD8+ T细胞和CD4+ T细胞浸润呈正相关。HTRA1可以作为OS预后和免疫治疗的潜在生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular and Cellular Probes 生物-生化研究方法

CiteScore

6.80

自引率

0.00%

发文量

审稿时长

16 days

期刊介绍： MCP - Advancing biology throughâ€“omics and bioinformatic technologies wants to capture outcomes from the current revolution in molecular technologies and sciences. The journal has broadened its scope and embraces any high quality research papers, reviews and opinions in areas including, but not limited to, molecular biology, cell biology, biochemistry, immunology, physiology, epidemiology, ecology, virology, microbiology, parasitology, genetics, evolutionary biology, genomics (including metagenomics), bioinformatics, proteomics, metabolomics, glycomics, and lipidomics. Submissions with a technology-driven focus on understanding normal biological or disease processes as well as conceptual advances and paradigm shifts are particularly encouraged. The Editors welcome fundamental or applied research areas; pre-submission enquiries about advanced draft manuscripts are welcomed. Top quality research and manuscripts will be fast-tracked.