A Promising Esophageal Cancer Prognostic Signature of Ferroptosis-Related LncRNA to Predict Immune Scenery and Immunotherapy Response

Abstract

Purpose Ferroptosis and long non-coding RNA (lncRNA) expression signatures have been associated with the clinical progression and immune-contexture of different solid tumors. The study aimed to identify a prognostic signature of ferroptosis-related lncRNAs (falncRNAs) to forecast the immune scenery and immunotherapy response in esophageal cancer (EC). Patients and Methods Gene expression profiles of EC were extracted from The Cancer Genome Atlas (TCGA) database, and ferroptosis-related genes were downloaded from the FerrDb database, which identified differentially expressed falncRNAs (DEfalncRNAs) via differential analysis. DEfalncRNA pairs associated with prognosis were identified by constructing a matrix, univariate and least absolute shrinkage and selection operator (LASSO) analysis. The prognostic signature was constructed by multivariate analysis. We appraised the forecasting capability of prognostic signature in survival, clinicopathological features, immune landscape, efficacy of immunotherapy, and drug sensitivity. The potential molecular mechanism of signature was investigated by gene set enrichment analysis (GSEA). Results We obtained 18 DEfalncRNA pairs to define a novel prognostic signature that was determined on a discovery cohort of 158 tumor samples and 11 adjacent normal tissues from TCGA and internally validated, with the definition of high- vs low-risk groups based on 3 years overall survival. We demonstrated that the high- vs low-risk groups differed for clinical parameters and computationally predicted drug sensitivity and tumor immune contexture, with the high-risk group having worse survival, more aggressive disease (node involvement, metastasis), reduced drug sensitivity, higher tumor mutation load, and gene signatures of infiltration of pro-tumoral immune cell subsets. The GSEA results revealed that ferroptosis and immunoregulatory pathways were significantly enriched in the high-risk group. Conclusion The prognostic signature based on falncRNAs has the potential to forecast the survival, immune scenery, efficacy of immunotherapy, and drug sensitivity of EC, which is helpful for clinical prediction and individualized treatment.

A Novel Ferroptosis-Related Gene Signature to Predict Prognosis of Esophageal Carcinoma

“…e protumor or antitumor state of immune cell in ltration in cancers is crucial for the e cacy of cancer treatment [48]. Recently, immunotherapy with immune checkpoint inhibitors has completely reversed the traditional treatment of ESCA [49]. In this study, the complex value was positively correlated with macrophage M0, and myeloid dendritic cell activated while negatively correlated with T cell CD4+ memory resting, T cell regulatory (Tregs), and mast cell activated.…”

Bioinformatic Analyses of the Ferroptosis-Related lncRNAs Signature for Ovarian Cancer

“…As for OC, lncRNA-based prognostic signatures have been reported in previous investigations ( Li et al, 2021 ; Pan and Bi, 2021 ). There are also lncRNA-based prognostic signatures for other cancers, such as breast cancer ( Li et al, 2020b ; Ma et al, 2020 ), glioma ( Lin et al, 2020 ), bladder urothelial carcinoma ( Sun et al, 2020 ), colorectal cancer ( Sun et al, 2020 ; Zhang et al, 2021 ), esophageal cancer ( Liu et al, 2021 ). To our knowledge, our study is the initial to identify and comprehensively analyze the ferroptosis-related lncRNAs signature for OC, providing a promising strategy for guiding individual therapy and improving prognosis prediction, and has important clinical implication.…”

The role of ferroptosis in esophageal cancer

“…Liu et al [ 54 ] obtained 18 pairs of differentially expressed ferroptosis-related long non-coding RNAs(DEfalncRNAs)by analyzing tumor samples and normal tissues, and established prognostic characteristic models. Through statistical analysis, they believed that it was possible to predict the survival expectation, immunotherapy effect and drug sensitivity of EC patients, which could contribute to individualized treatment and clinical prediction.…”

“…Although many studies have confirmed the close relationship between ferroptosis and various diseases, the role of ferroptosis in EC is still in its infancy. At present, the research of ferroptosis in the field of EC is still focused on using genetic data from the database to screen ferroptosis-related genes to predict the prognosis of patients with EC [ 49 , 50 , 54 ]. At the same time, these findings are helpful for patients to judge immunotherapy and drug sensitivity, and indicate that the immune process of EC is highly correlated with ferroptosis, which may be a key direction of future research.…”