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自噬相关特征分析确定了两种不同亚型,用于评估卵巢癌的肿瘤免疫微环境和预测预后。

Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer.

作者信息

Chen Xingyu, Lan Hua, He Dong, Wang Zhanwang, Xu Runshi, Yuan Jing, Xiao Mengqing, Zhang Yao, Gong Lian, Xiao Songshu, Cao Ke

机构信息

Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, China.

Department of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, Changsha, China.

出版信息

Front Oncol. 2021 May 10;11:616133. doi: 10.3389/fonc.2021.616133. eCollection 2021.

Abstract

Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in OC. Here, we obtained ARGs from the MSigDB database and downloaded the expression profile of OC from TCGA database. The k-means unsupervised clustering method was used for clustering, and two subclasses of OC (cluster A and cluster B) were identified. SsGSEA method was used to quantify the levels of infiltration of 24 subtypes of immune cells. Metascape and GSEA were performed to reveal the differential gene enrichment in signaling pathways and cellular processes of the subtypes. We found that patients in cluster A were significantly associated with higher immune infiltration and immune-associated signaling pathways. Then, we established a risk model by LASSO Cox regression. ROC analysis and Kaplan-Meier analysis were applied for evaluating the efficiency of the risk signature, patients with low-risk got better outcomes than those with high-risk in overall survival. Finally, ULK2 and GABARAPL1 expression was further validated in clinical samples. In conclusion, Our study constructed an autophagy-related prognostic indicator, and identified two promising targets in OC.

摘要

卵巢癌(OC)是最致命的妇科恶性肿瘤之一。自噬与肿瘤免疫微环境之间的相互作用具有临床重要性。因此,有必要探索与自噬相关基因(ARGs)相关的可靠生物标志物,用于OC的风险分层。在此,我们从MSigDB数据库中获取ARGs,并从TCGA数据库下载OC的表达谱。使用k均值无监督聚类方法进行聚类,识别出OC的两个亚类(A簇和B簇)。采用单样本基因集富集分析(SsGSEA)方法量化24种免疫细胞亚型的浸润水平。进行Metascape和基因集富集分析(GSEA)以揭示亚类在信号通路和细胞过程中的差异基因富集情况。我们发现A簇中的患者与更高的免疫浸润和免疫相关信号通路显著相关。然后,我们通过LASSO Cox回归建立了一个风险模型。应用受试者工作特征(ROC)分析和Kaplan-Meier分析来评估风险特征的效率,低风险患者在总生存期的结局优于高风险患者。最后,在临床样本中进一步验证了ULK2和GABARAPL1的表达。总之,我们的研究构建了一个与自噬相关的预后指标,并在OC中鉴定出两个有前景的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/016f/8141647/044d77a112c9/fonc-11-616133-g001.jpg

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