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综合多组学特征揭示与铜死亡相关的枢纽基因以预测卵巢癌的预后和临床疗效。

Integrated multiomics characterization reveals cuproptosis-related hub genes for predicting the prognosis and clinical efficacy of ovarian cancer.

作者信息

Xiaorong Yang, Lu Xu, Fangyue Xu, Chao Xu, Jun Gao, Qiang Wen

机构信息

Department of Gynecologic Oncology, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Nanchang, China.

Department of Integrated Chinese and Western Medicine, Zhejiang Cancer Hospital, Hangzhou, China.

出版信息

Front Immunol. 2024 Nov 12;15:1452294. doi: 10.3389/fimmu.2024.1452294. eCollection 2024.

Abstract

BACKGROUND

As a prevalent malignancy in women, ovarian cancer (OC) presents a challenge in clinical practice because of its poor prognosis and poor therapeutic efficacy. The mechanism by which cuproptosis activity is accompanied by immune infiltration in OC remains unknown. Here, we investigated cuproptosis-related OC subtypes and relevant immune landscapes to develop a risk score (RS) model for survival prediction.

METHODS

Cuproptosis-related genes (CRGs) were identified to construct molecular subtypes via an unsupervised clustering algorithm based on the expression profiles of survival-related CRGs in the GEO database. Single-cell datasets were used to estimate immune infiltration among subtypes. The RS oriented from molecular subtypes was developed via LASSO Cox regression in the TCGA OC dataset and independently validated in the GEO and TCGA datasets. Hub markers from RS were identified in tissues and cell lines. The function of the key gene from RS was identified .

RESULTS

We investigated cuproptosis activity and immune infiltration to establish three clinical subtypes of OC based the differentially expressed genes (DEGs) from CRGs to create an RS model validated for clinical efficacy and prognosis. Six hub genes from the RS served as ongenic markers in OC tissues and cell lines. The function of GAS1 in the RS model revealed that it exerts oncogenic effects.

CONCLUSIONS

Our study provides a novel RS model including 6 hub genes associated with cuproptosis and immune infiltration to predict OC prognosis as well as clinical efficacy.

摘要

背景

卵巢癌(OC)作为女性中一种常见的恶性肿瘤,因其预后差和治疗效果不佳,在临床实践中构成了挑战。铜死亡活性伴随OC免疫浸润的机制尚不清楚。在此,我们研究了与铜死亡相关的OC亚型和相关免疫格局,以建立一个用于生存预测的风险评分(RS)模型。

方法

基于GEO数据库中与生存相关的铜死亡相关基因(CRG)的表达谱,通过无监督聚类算法鉴定CRG以构建分子亚型。单细胞数据集用于估计各亚型间的免疫浸润情况。在TCGA OC数据集中通过LASSO Cox回归建立源于分子亚型的RS,并在GEO和TCGA数据集中进行独立验证。在组织和细胞系中鉴定RS的核心标志物。确定RS关键基因的功能。

结果

我们研究了铜死亡活性和免疫浸润,基于CRG的差异表达基因(DEG)建立了OC的三种临床亚型,以创建一个经临床疗效和预后验证的RS模型。RS中的六个核心基因在OC组织和细胞系中作为致癌标志物。RS模型中GAS1的功能表明它具有致癌作用。

结论

我们的研究提供了一种新的RS模型,包括6个与铜死亡和免疫浸润相关的核心基因,用于预测OC的预后以及临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c803/11588705/744bbdefee73/fimmu-15-1452294-g001.jpg

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