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

IF 3.1 4区医学 Q3 IMMUNOLOGY

Immunity, Inflammation and Disease Pub Date : 2024-10-11 DOI:10.1002/iid3.70037

Guang-hua Nie, Cheng-yi Liu, Zhao Tian

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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.

Abstract Image

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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学作用。

背景：软组织肉瘤（STS软组织肉瘤（STS）是一种多发性恶性肿瘤，常发生于青少年，预后较差。基底膜作为一种古老的细胞基质，最近被证实在丰富的肿瘤发生过程中起着至关重要的作用。基底膜相关基因与 STS 之间的关系仍然未知：方法：采用共识聚类确定与不同表达的基底膜相关基因有关的亚组。利用 Cox 和最小绝对缩减及选择算子回归分析构建了这一新型特征。然后，我们建立了包括风险评分和现有临床特征在内的提名图和校准曲线。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通路和肿瘤免疫微环境：结果：建立了由八个基底膜相关基因组成的预后预测特征。Kaplan-Meier生存曲线显示，高风险组患者预后较差。独立分析表明，该风险模型可作为独立的预后预测指标。我们在验证数据集中验证了我们的特征的准确性。此外，基因组富集分析和免疫微环境分析表明，低风险评分的患者富集了一些与免疫相关的通路。最后，体外实验显示，这些特征基因在STS细胞中的表达水平存在明显差异，PSAT1可促进STS的恶性行为：结论：新的特征基因是预测 STS 预后的有效指标。本研究可能会改善 STS 的预后，并在未来加强 STS 的个体化治疗。

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

Immunity, Inflammation and Disease Medicine-Immunology and Allergy

CiteScore

3.60

自引率

0.00%

发文量

146

审稿时长

8 weeks

期刊介绍： Immunity, Inflammation and Disease is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research across the broad field of immunology. Immunity, Inflammation and Disease gives rapid consideration to papers in all areas of clinical and basic research. The journal is indexed in Medline and the Science Citation Index Expanded (part of Web of Science), among others. It welcomes original work that enhances the understanding of immunology in areas including: • cellular and molecular immunology • clinical immunology • allergy • immunochemistry • immunogenetics • immune signalling • immune development • imaging • mathematical modelling • autoimmunity • transplantation immunology • cancer immunology