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Dissecting the ferroptosis-related prognostic biomarker and immune microenvironment of driver gene-negative lung cancer

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机构: [1]Guangzhou Univ Chinese Med, Clin Med Sch 2, Guangzhou 510405, Peoples R China [2]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Tradit Chinese Med, Dept Oncol, Affiliated Hosp 2, Guangzhou 510120, Peoples R China [3]Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou 510120, Peoples R China [4]Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangzhou 510120, Peoples R China [5]Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou 510120, Peoples R China
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关键词: Ferroptosis EGFR ALK (WT) low PD-L1 expression NSCLC prognosis immune microenvironment

摘要:
Despite significant advances in targeted and immune therapy for non-small cell lung cancer (NSCLC), effective therapies for wild-type epidermal growth factor receptor/anaplastic lymphoma kinase (EGFR/ALK(WT)) with low expression of programmed death ligand-1 (PD-L1) NSCLC remain elusive. Numerous studies have shown that ferroptosis plays an essential role in antitumor activity. To identify the molecular regulation patterns associated with ferroptosis, 351 EGFR/ALK(WT) NSCLC samples with low-level PD-L1 were extracted from The Cancer Genome Atlas (TCGA) and clustered using the k-means clustering technique. The two clusters associated with ferroptosis showed significantly different prognoses. In total, 169 differential expression genes (DEGs) were identified. Cluster differential analysis revealed that Cluster 1 had a significantly poorer overall survival (OS) and was associated with more negative immune regulation. In addition, TCGA samples were randomly assigned in a 7:3 ratio to a training group or testing group. A signature of eight genes associated with ferroptosis was established in the training cohort using DEGs and validated in the test cohort and three independent cohorts (GSE72049, GSE41271, and GSE50081). The 5-year area under the curve (AUC) was 0.713, which was significantly higher than that of other predictors, including TNM stage and age. Furthermore, the risk score was associated with immune function, immune infiltration, and immunotherapy response, with high-risk patients having a worse prognosis, an immune-suppressing phenotype, and a poor response to immune checkpoint inhibitors. This study aims to contribute to our understanding of the biological role of ferroptosis in EGFR/ALK(WT) NSCLC with low-level PD-L1, laying the groundwork for the development of novel therapeutic strategies.

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基金编号: 2017B030314166 2020B1212030006

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验
最新[2025]版:
大类 | 4 区 医学
小类 | 4 区 医学:研究与实验
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出版当年[2020]版:
Q3 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q2 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Guangzhou Univ Chinese Med, Clin Med Sch 2, Guangzhou 510405, Peoples R China
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通讯机构: [1]Guangzhou Univ Chinese Med, Clin Med Sch 2, Guangzhou 510405, Peoples R China [2]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Tradit Chinese Med, Dept Oncol, Affiliated Hosp 2, Guangzhou 510120, Peoples R China [3]Guangdong Hong Kong Macau Joint Lab Chinese Med &, Guangzhou 510120, Peoples R China [4]Guangdong Prov Key Lab Clin Res Tradit Chinese Me, Guangzhou 510120, Peoples R China [5]Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou 510120, Peoples R China
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