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高尔基器相关基因的分子特征表明骨肉瘤的预后和免疫浸润。

Molecular characterization of Golgi apparatus-related genes indicates prognosis and immune infiltration in osteosarcoma.

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

Institute of Orthopedics of Jiangxi Province, Nanchang 330006, Jiangxi, China.

出版信息

Aging (Albany NY). 2024 Mar 7;16(6):5249-5263. doi: 10.18632/aging.205645.

Abstract

BACKGROUND

The Golgi apparatus (GA) is crucial for protein synthesis and modification, and regulates various cellular processes. Dysregulation of GA can lead to pathological conditions like neoplastic growth. GA-related genes (GARGs) mutations are commonly found in cancer, contributing to tumor metastasis. However, the expression and prognostic significance of GARGs in osteosarcoma are yet to be understood.

METHODS

Gene expression and clinical data of osteosarcoma patients were obtained from the TARGET and GEO databases. A consensus clustering analysis identified distinct molecular subtypes based on GARGs. Discrepancies in biological processes and immunological features among the subtypes were explored using GSVA, ssGSEA, and Metascape analysis. A GARGs signature was constructed using Cox regression. The prognostic value of the GARGs signature in osteosarcoma was evaluated using Kaplan-Meier curves and a nomogram.

RESULTS

Two GARG subtypes were identified, with Cluster A showing better prognosis, immunogenicity, and immune cell infiltration than Cluster B. A novel risk model of 3 GARGs was established using the TARGET dataset and validated with independent datasets. High-risk patients had poorer overall survival, and the GARGs signature independently predicted osteosarcoma prognosis. Combining risk scores and clinical characteristics in a nomogram improved prediction performance. Additionally, we discovered Stanniocalcin-2 (STC2) as a significant prognostic gene highly expressed in osteosarcoma and potential disease biomarker.

CONCLUSIONS

Our study revealed that patients with osteosarcoma can be divided into two GARGs subgroups. Furthermore, we have developed a GARGs prognostic signature that can accurately forecast the prognosis of osteosarcoma patients.

摘要

背景

高尔基体(GA)在蛋白质合成和修饰中至关重要,调节着各种细胞过程。GA 的失调可导致肿瘤生长等病理状况。GA 相关基因(GARGs)突变常见于癌症,促进肿瘤转移。然而,GARGs 在骨肉瘤中的表达和预后意义尚不清楚。

方法

从 TARGET 和 GEO 数据库中获取骨肉瘤患者的基因表达和临床数据。基于 GARGs 的共识聚类分析确定了不同的分子亚型。使用 GSVA、ssGSEA 和 Metascape 分析探讨了亚型之间生物学过程和免疫特征的差异。使用 Cox 回归构建 GARGs 特征。使用 Kaplan-Meier 曲线和诺莫图评估 GARGs 特征在骨肉瘤中的预后价值。

结果

确定了两种 GARG 亚型,与 Cluster B 相比,Cluster A 具有更好的预后、免疫原性和免疫细胞浸润。使用 TARGET 数据集建立了一个新的 3 个 GARGs 风险模型,并在独立数据集上进行了验证。高风险患者的总体生存率较差,GARGs 特征独立预测骨肉瘤预后。在诺莫图中结合风险评分和临床特征可提高预测性能。此外,我们发现 Stanniocalcin-2(STC2)是一种在骨肉瘤中高度表达的有意义的预后基因,也是一种有潜力的疾病生物标志物。

结论

我们的研究表明,骨肉瘤患者可以分为两个 GARGs 亚组。此外,我们开发了一种 GARGs 预后特征,可以准确预测骨肉瘤患者的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4beb/11006476/f059b5fce72e/aging-16-205645-g001.jpg

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