Identification and Validation of Ferroptosis-Related LncRNA Signatures as a Novel Prognostic Model for Colon Cancer

Frontiers in Immunology

Jing Chou¹  Changwei Lin¹  Fei Long¹  Yi Zhang¹  Zhixing Lu¹  Liang Li¹  Gui Hu¹  Zhiwei Wu¹  Runliu Wu¹  Xiaorong Li¹  Min Ma¹  Kaiyan Yang¹  Lihua Huang³ 

[1] Department of Gastrointestinal Surgery, The Third XiangYa Hospital of Central South University, Changsha, China;Department of General Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China;School of Life Sciences, Central South University, Changsha, China;

关键词: lncRNAs;    ferroptosis;    colorectal cancer;    prognostic signature;    immune microenvironment;   

DOI  :  10.3389/fimmu.2021.783362

来源: DOAJ

【 摘 要 】

BackgroundFerroptosis is a newly defined form of programmed cell death that plays an important role in many cancers. However, ferroptosis-related lncRNAs (FRLs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic FRL signature in colon cancer and explore its potential molecular function.MethodsRNA-seq data and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database, and a list of ferroptosis-related genes was extracted from the FerrDb website. Analysis of differentially expressed FRLs was performed using the ‘limma’ package in R software. By implementing coexpression analysis and univariate Cox analysis, we then identified prognostic FRLs. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 4 FRLs. We evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune landscape, somatic mutation and drug sensitivity were explored. Finally, in vitro experiments were conducted to validate the functions of AP003555.1 and AC000584.1.ResultsA 4-FRL signature was constructed. Two risk groups were classified based on the risk score calculated by this signature. The signature-based risk score exhibited a more powerful capacity for survival prediction than traditional clinicopathological features in colon patients. Additionally, we observed a significant difference in immune cells, such as CD4+ and CD8+ T cells and macrophages, between the two groups. Moreover, the high-risk group exhibited lower IC50 values for certain chemotherapy drugs, such as cisplatin, docetaxel, bleomycin or axitinib. Finally, the in vitro experiments showed that ferroptosis processes were suppressed after AP003555.1 and AC000584.1 knockdown.ConclusionThe proposed 4-FRL signature is a promising biomarker to predict clinical outcomes and therapeutic responses in colon cancer patients.

【 授权许可】

Unknown