The Ferroptosis-Related Noncoding RNA Signature as a Novel Prognostic Biomarker in the Tumor Microenvironment, Immunotherapy, and Drug Screening of Gastric Adenocarcinoma

Abstract

BackgroundFerroptosis is a new type of cell death different from apoptosis, necrosis, autophagy, and pyroptosis. This study aimed to explore the relationship between ferroptosis-related noncoding RNA (ncRNA) and gastric adenocarcinoma with regard to immunity and prognosis.MethodsFerroptosis-related ncRNA expression profiles and clinical pathology and overall survival information were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database. The ferroptosis-related ncRNA signature was identified by Cox regression analysis and the least absolute shrinkage and selection operator analysis. The survival analysis, receiver operating characteristic (ROC) analysis, and decision curve analysis were adopted to evaluate the prognostic prediction performance of the signature. The correlation between risk and multiple clinical characteristics was analyzed using the chi-square test. The Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for mining functions and pathways. The CIBERSORT, ssGSEA, and ESTIMATE algorithms were used to assess immune infiltration and the tumor microenvironment. The response of immunotherapy was predicted using the Submap algorithm, and the Connectivity Map and the ridge regression model were used to screen and evaluate drugs.ResultsA carcinogenic risk signature was constructed using five ferroptosis-related ncRNAs. It showed an extraordinary ability to predict the prognoses of patients with gastric adenocarcinoma [area under the ROC curve (AUC) after 6 years = 0.689; GSE84426, AUC after 6 years = 0.747]. The lower ferroptosis potential level and lower tumor mutation burden were related to the poor prognoses of patients. The high-risk group had more immune cell recruitment, and the overall effect of the anti-immune checkpoint immunotherapy was not as good as that of the low-risk group. The high- and low-risk groups were enriched in tumor- and immune-related pathways, respectively. The screened antitumor drugs, such as genistein, guanabenz, and betulinic acid, improved the survival of the patients.ConclusionsThe ferroptosis-related ncRNA signature is a potential carcinogenic prognostic biomarker of gastric adenocarcinoma.

Prognostic Implications and Immune Infiltration Characteristics of Chromosomal Instability-Related Dysregulated CeRNA in Lung Adenocarcinoma

“…The TIDE and IPS scores exhibited differences in patients distinguished by the CRDC score, which displayed that LUAD patients with decreased CRDC risk scores had lower immune dysfunction and exclusion score as well as more possibility to benefit from immune checkpoint therapy ( Figures 7H,I ). In addition, based on the common subtype comparison analysis between two CRDC groups and melanoma samples with the information of immunotherapy reaction ( Roh et al, 2017 ; Chen et al, 2021 ), we could infer that patients with low CRDC risk were more likely to respond to anti-PD1 therapy (Bonferroni-corrected p = 0.044), yet high CRDC group may be resistant to this form of treatment (Nominal p = 0.042, Figure 7J ). In brief, we revealed that CRDC had relevance to immune characteristics, and patients with low CRDC risk exhibited greater immunocompetence than those with high risk.…”

Development and Validation of Prognostic Model for Lung Adenocarcinoma Patients Based on m6A Methylation Related Transcriptomics

“…Immune checkpoints, negative regulators of immune activation, can downregulate the immune state of the body and limit antitumor responses ( 35 , 36 ). Tumor Immune Dysfunction and Rejection (TIDE) is a computational framework developed to assess the potential of tumor immune escape from gene-expressed cancer samples and to measure the responsiveness of immune checkpoint inhibitors ( 37 , 38 ).…”

Ferroptosis and its Role in Gastric Cancer

“…Interestingly, tumor cells and their surrounding microenvironment can be shaped by varying degrees of ferroptosis activation ( Zavros, 2017 ; Xiao et al, 2021 ). It has been found that ferroptosis serves as an important factor in the formation of the TME in GC ( Jiang et al, 2021b ; Wang F. et al, 2021 ; Chen et al, 2021b ). In addition, numerous studies have demonstrated that dying cells, including ferroptotic cancer cells, communicate with the immune cells in the TME via a series of signals ( Friedmann Angeli et al, 2019 ).…”