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全面分析基底膜相关基因在软组织肉瘤中的预后和免疫作用。

Comprehensive analysis of prognostic and immunological role of basement membrane-related genes in soft tissue sarcoma.

机构信息

Department of Foot and Ankle Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

Department of Hand Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

出版信息

Immun Inflamm Dis. 2024 Oct;12(10):e70037. doi: 10.1002/iid3.70037.

Abstract

BACKGROUND

Soft tissue sarcoma (STS) represents highly multifarious malignant tumors that often occur in adolescents and have a poor prognosis. The basement membrane, as an ancient cellular matrix, was recently proven to play a vital role in developing abundant tumors. The relationship between basement membrane-related genes and STS remains unknown.

METHODS

Consensus clustering was employed to identify subgroups related to differentially expressed basement membrane-related genes. Cox and least absolute shrinkage and selection operator regression analyses were utilized to construct this novel signature. Then, we established a nomogram and calibration curve, including the risk score and available clinical characteristics. Finally, we carried out functional enrichment analysis and immune microenvironment analysis to investigate enriched pathways and the tumor immune microenvironment related to the novel signature.

RESULTS

A prognostic predictive signature consisting of eight basement membrane-related genes was established. Kaplan-Meier survival curves demonstrated that the patients in the high-risk group had a poor prognosis. Independent analysis illustrated that this risk model could be an independent prognostic predictor. We validated the accuracy of our signature in the validation data set. In addition, gene set enrichment analysis and immune microenvironment analysis showed that patients with low-risk scores were enriched in some pathways associated with immunity. Finally, in vitro experiments showed significantly differential expression levels of these signature genes in STS cells and PSAT1 could promote the malignant behavior of STS.

CONCLUSIONS

The novel signature is a promising prognostic predictor for STS. The present study may improve the prognosis and enhance individualized treatment for STS in the future.

摘要

背景

软组织肉瘤(STS)是一种高度异质性的恶性肿瘤,常发生于青少年,预后不良。基底膜作为一种古老的细胞基质,最近被证明在大量肿瘤的发生中起着至关重要的作用。基底膜相关基因与 STS 之间的关系尚不清楚。

方法

采用共识聚类方法识别与差异表达基底膜相关基因相关的亚组。采用 Cox 和最小绝对收缩和选择算子回归分析构建该新的特征。然后,我们建立了一个列线图和校准曲线,包括风险评分和可用的临床特征。最后,我们进行了功能富集分析和免疫微环境分析,以研究与新特征相关的富集途径和肿瘤免疫微环境。

结果

建立了一个由 8 个基底膜相关基因组成的预后预测特征。Kaplan-Meier 生存曲线表明,高风险组患者预后不良。独立分析表明,该风险模型可以作为独立的预后预测指标。我们在验证数据集验证了我们特征的准确性。此外,基因集富集分析和免疫微环境分析表明,低风险评分的患者在与免疫相关的一些途径中富集。最后,体外实验表明这些特征基因在 STS 细胞中的表达水平存在显著差异,PSAT1 可促进 STS 的恶性行为。

结论

该新特征是 STS 的一种有前途的预后预测指标。本研究可能会改善 STS 的预后,并为未来的 STS 提供个性化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2dec/11467964/5a6a91d3ebc9/IID3-12-e70037-g007.jpg

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