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通过生物信息学分析鉴定 G 蛋白偶联受体相关基因特征,构建卵巢癌预后风险模型。

Identification of a G-protein coupled receptor-related gene signature through bioinformatics analysis to construct a risk model for ovarian cancer prognosis.

机构信息

Clinical Medical College, Ningxia Medical University, Yinchuan, Ningxia, China.

Gynecology Department, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.

出版信息

Comput Biol Med. 2024 Aug;178:108747. doi: 10.1016/j.compbiomed.2024.108747. Epub 2024 Jun 18.

DOI:10.1016/j.compbiomed.2024.108747
PMID:38897150
Abstract

BACKGROUND

Ovarian cancer (OV) is a common malignant tumor of the female reproductive system with a 5-year survival rate of ∼30 %. Inefficient early diagnosis and prognosis leads to poor survival in most patients. G protein-coupled receptors (GPCRs, the largest family of human cell surface receptors) are associated with OV. We aimed to identify GPCR-related gene (GPCRRG) signatures and develop a novel model to predict OV prognosis.

METHOD

We downloaded data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognostic GPCRRGs were screened using least absolute shrinkage and selection operator (LASSO) Cox regression analysis, and a prognostic model was constructed. The predictive ability of the model was evaluated by Kaplan-Meier (K-M) survival analysis. The levels of GPCRRGs were examined in normal and OV cell lines using quantitative reverse-Etranscription polymerase chain reaction. The immunological characteristics of the high- and low-risk groups were analyzed using single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT.

RESULTS

Based on the risks scores, 17 GPCRRGs were associated with OV prognosis. CXCR4, GPR34, LGR6, LPAR3, and RGS2 were significantly expressed in three OV datasets and enabled accurate OV diagnosis. K-M analysis of the prognostic model showed that it could differentiate high- and low-risk patients, which correspond to poorer and better prognoses, respectively. GPCRRG expression was correlated with immune infiltration rates.

CONCLUSIONS

Our prognostic model elaborates on the roles of GPCRRGs in OV and provides a new tool for prognosis and immune response prediction in patients with OV.

摘要

背景

卵巢癌(OV)是一种常见的女性生殖系统恶性肿瘤,5 年生存率约为 30%。OV 早期诊断和预后效果不理想,导致大多数患者生存状况较差。G 蛋白偶联受体(GPCRs,人类细胞表面受体中最大的家族)与 OV 相关。本研究旨在鉴定 GPCR 相关基因(GPCRRG)特征,并构建一种新的模型来预测 OV 预后。

方法

我们从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载数据。采用最小绝对值收缩和选择算子(LASSO)Cox 回归分析筛选预后 GPCRRGs,并构建预后模型。通过 Kaplan-Meier(K-M)生存分析评估模型的预测能力。采用实时定量逆转录聚合酶链反应检测正常和 OV 细胞系中 GPCRRGs 的水平。采用单样本基因集富集分析(ssGSEA)和 CIBERSORT 分析高低风险组的免疫特征。

结果

基于风险评分,鉴定出 17 个与 OV 预后相关的 GPCRRGs。CXCR4、GPR34、LGR6、LPAR3 和 RGS2 在三个 OV 数据集的表达水平存在显著差异,可准确诊断 OV。预后模型的 K-M 分析表明,该模型能够区分高低风险患者,低风险患者预后较好,而高风险患者预后较差。GPCRRG 表达与免疫浸润率相关。

结论

本研究构建的预后模型阐述了 GPCRRGs 在 OV 中的作用,为 OV 患者的预后和免疫反应预测提供了新的工具。

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