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构建用于预测肺腺癌患者生存的新型铁死亡相关基因特征

Construction of a Novel Ferroptosis-Related Gene Signature for Predicting Survival of Patients With Lung Adenocarcinoma.

作者信息

Song Xiaojie, Wu Liqun, Wang Guangqiang, Liu Baoyi, Zhu Wenyong

机构信息

Department of Respiratory Medicine, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.

Department of Thoracic Surgery, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University, Qingdao, China.

出版信息

Front Oncol. 2022 Mar 3;12:810526. doi: 10.3389/fonc.2022.810526. eCollection 2022.

Abstract

Lung adenocarcinoma (LUAD) is the most diagnosed subtype of lung cancer; ferroptosis is widely involved in the pathological cell death associated with various cancers, including lung cancer. However, the comprehensive relationship between ferroptosis and LUAD is little known in molecular levels until now. In the present study, 513 LUAD patients could be aggregated into three clusters by consensus clustering based on RNA sequencing data of 291 ferroptosis-related genes (FRGs) in The Cancer Genome Atlas (TCGA) database; cluster2 had significant survival advantage compared to the other two clusters. A novel prognostic model of 8 differential FRGs was constructed to effectively divide LUAD patients into high- or low-risk group according to the risk scores by the Cox and LASSO regression analyses. The overall survival of LUAD patients in the high-risk group was significantly worse in the TCGA and GEO cohorts. Moreover, patients with radiation therapy or high clinical stage had obviously higher risk scores. We validated the differential mRNA and protein expression of four FRGs in paired tumor and normal samples from our clinical cohort. Our study constructed a novel FRG signature to predict the prognosis of LUAD patients, which might provide a new prognostic tool and potential therapeutic targets for LUAD.

摘要

肺腺癌(LUAD)是肺癌中最常被诊断出的亚型;铁死亡广泛参与包括肺癌在内的多种癌症相关的病理性细胞死亡。然而,截至目前,铁死亡与肺腺癌在分子水平上的全面关系仍鲜为人知。在本研究中,基于癌症基因组图谱(TCGA)数据库中291个铁死亡相关基因(FRG)的RNA测序数据,通过一致性聚类可将513例肺腺癌患者聚为三个簇;与其他两个簇相比,簇2具有显著的生存优势。通过Cox和LASSO回归分析,构建了一个由8个差异FRG组成的新型预后模型,以根据风险评分有效地将肺腺癌患者分为高风险组或低风险组。在TCGA和GEO队列中,高风险组肺腺癌患者的总生存期明显更差。此外,接受放射治疗或临床分期较高的患者风险评分明显更高。我们在临床队列的配对肿瘤和正常样本中验证了4个FRG的差异mRNA和蛋白质表达。我们的研究构建了一种新型FRG特征来预测肺腺癌患者的预后,这可能为肺腺癌提供一种新的预后工具和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a9e/8928751/cff1ea5e4f1e/fonc-12-810526-g001.jpg

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