机构:[1]Guangzhou Univ Chinese Med, Clin Med Sch 2, Guangzhou 510405, Peoples R China广东省中医院[2]Guangzhou Univ Chinese Med, Guangdong Prov Hosp Tradit Chinese Med, Dept Oncol, Affiliated Hosp 2, Guangzhou 510120, Peoples R China大德路总院肿瘤科广东省中医院[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广东省中医院[5]Guangzhou Univ Chinese Med, State Key Lab Dampness Syndrome Chinese Med, Affiliated Hosp 2, Guangzhou 510120, Peoples R China广东省中医院
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.
基金:
Science and Technology Planning Project of Guangdong Province [2017B030314166]; 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund (Guangdong-Hong KongMacau Joint Lab) [2020B1212030006]
第一作者机构:[1]Guangzhou Univ Chinese Med, Clin Med Sch 2, Guangzhou 510405, Peoples R China
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Zhou Rui,Ma Hao-Chuan,Liu Yi-Hong,et al.Dissecting the ferroptosis-related prognostic biomarker and immune microenvironment of driver gene-negative lung cancer[J].EXPERIMENTAL BIOLOGY AND MEDICINE.2022,247(16):1447-1465.doi:10.1177/15353702221102872.
APA:
Zhou, Rui,Ma, Hao-Chuan,Liu, Yi-Hong,Chen, Xian,Chang, Xue-Song...&Zhang, Hai-Bo.(2022).Dissecting the ferroptosis-related prognostic biomarker and immune microenvironment of driver gene-negative lung cancer.EXPERIMENTAL BIOLOGY AND MEDICINE,247,(16)
MLA:
Zhou, Rui,et al."Dissecting the ferroptosis-related prognostic biomarker and immune microenvironment of driver gene-negative lung cancer".EXPERIMENTAL BIOLOGY AND MEDICINE 247..16(2022):1447-1465