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基于γ-氨基丁酸特征的新型风险评分模型可预测乳腺癌患者的生存预后。

A novel risk score model based on gamma-aminobutyric acid signature predicts the survival prognosis of patients with breast cancer.

作者信息

Yang Liping, Zhu Jin, Wang Lieliang, He Longbo, Gong Yi, Luo Qingfeng

机构信息

Department of Breast Cancer Surgery, Jiangxi Cancer Hospital, Nanchang, China.

Department of Pathology, Jiangxi Cancer Hospital, Nanchang, China.

出版信息

Front Oncol. 2023 Mar 8;13:1108823. doi: 10.3389/fonc.2023.1108823. eCollection 2023.

Abstract

BACKGROUND

Gamma-aminobutyric acid (GABA) participates in the migration, differentiation, and proliferation of tumor cells. However, the GABA-related risk signature has never been investigated. Hence, we aimed to develop a reliable gene signature based on GABA pathways-related genes (GRGs) to predict the survival prognosis of breast cancer patients.

METHODS

GABA-related gene sets were acquired from the MSigDB database, while mRNA gene expression profiles and corresponding clinical data of breast cancer patients were downloaded from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Univariate Cox regression analysis was used to identify prognostic-associated GRGs. Subsequently, LASSO analysis was applied to establish a risk score model. We also constructed a clinical nomogram to perform the survival evaluation. Besides, ESTIMATE and ssGSEA algorithms were used to assess the immune cell infiltration among the risk score subgroups.

RESULTS

A GRGs-related risk score model was constructed in the TCGA cohort, and validated in the GSE21653 cohort. The risk score was significantly related to the overall survival of breast cancer patients, which could predict the survival prognosis of breast cancer patients independently of other clinical features. Breast cancer patients in the low-risk score group exhibited higher immune cell infiltration levels.

CONCLUSION

A novel prognostic model containing five GRGs could accurately predict the survival prognosis and immune infiltration of breast cancer patients. Our findings provided a novel insight into investigating the immunoregulation roles of GRGs.

摘要

背景

γ-氨基丁酸(GABA)参与肿瘤细胞的迁移、分化和增殖。然而,从未有人研究过与GABA相关的风险特征。因此,我们旨在基于GABA通路相关基因(GRGs)开发一种可靠的基因特征,以预测乳腺癌患者的生存预后。

方法

从MSigDB数据库获取GABA相关基因集,同时从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)数据库下载乳腺癌患者的mRNA基因表达谱及相应临床数据。采用单变量Cox回归分析来识别与预后相关的GRGs。随后,应用LASSO分析建立风险评分模型。我们还构建了临床列线图以进行生存评估。此外,使用ESTIMATE和ssGSEA算法评估风险评分亚组之间的免疫细胞浸润情况。

结果

在TCGA队列中构建了一个与GRGs相关的风险评分模型,并在GSE21653队列中进行了验证。风险评分与乳腺癌患者的总生存期显著相关,其能够独立于其他临床特征预测乳腺癌患者的生存预后。低风险评分组的乳腺癌患者表现出更高的免疫细胞浸润水平。

结论

一个包含五个GRGs的新型预后模型能够准确预测乳腺癌患者的生存预后和免疫浸润情况。我们的研究结果为研究GRGs的免疫调节作用提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b17/10031029/706cc1e99184/fonc-13-1108823-g001.jpg

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