A ferroptosis-related lncRNAs signature for prognosis prediction and its relationship with immune microenvironment in colon adenocarcinoma

Abstract

Abstract Objective The present study aimed to develop a prognostic ferroptosis-related long noncoding RNAs (lncRNAs) signature and to investigate its potential relationship with clinical characteristics and immune microenvironment in patients with colon adenocarcinoma (COAD). Methods Clinical information and RNA sequencing data were downloaded from The Cancer Genome Atlas (TCGA) database. Genes associated with ferroptosis were retrieved from the FerrDb database. Pearson’s correlation analysis was performed for the retrieved data, and differentially expressed ferroptosis-related lncRNAs (frlncRNAs) were screened out. A prognostic frlncRNAs signature was established based on the results of univariate Cox regression analysis and the least absolute shrinkage and selection operator algorithm. Survival analysis and receiver operating characteristic curve analysis were conducted to evaluate the prognostic efficacy of this signature. Gene set enrichment analysis (GSEA), somatic mutation analysis, drug sensitivity analysis, and immune analysis were performed. Quantitative real-time PCR was then used to confirm the expression of lncRNAs, and the regulatory functions of the screened lncRNAs LINC01138 and LINC01857 in ferroptosis were assessed. Results Eleven frlncRNAs were identified from the databases. A prognostic signature was constructed, and the risk score was calculated. Patients were classified into high-and low-risk groups according to their risk score. The prognostic signature showed a high efficacy for survival prediction, and the risk score was confirmed as an independent prognostic factor. GSEA showed differences between the two groups in terms of specific pathways involved in immune response, cell adhesion, mitochondrial function, and energy metabolism. Moreover, the high- and low-risk groups showed a significant difference in somatic mutation status such as that of TP53 gene. Patients in the high-risk group exhibited lower half-inhibitory concentration (IC50) values for cisplatin, bleomycin, gefitinib, veliparib, rapamycin, AZD8055, MK-2206, and Bay61-3606 and a higher IC50 value for sorafenib. Immune status and response of the patients to immunotherapy were also associated with the risk signature. The experiments also showed that LINC01138 and LINC01857 regulated ferroptosis processes in COAD. Conclusion The prognostic signature of frlncRNAs developed in this study facilitate the clinical diagnosis and treatment of patients with COAD and may enable to study the deeper functional mechanisms of frlncRNAs in immune microenvironment in COAD.