Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer

Abstract

Ferroptosis is associated with the prognosis and therapeutic responses of patients with various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed the combined effects of ferroptosis and lncRNAs on the prognosis and therapy of stomach cancer. In this study, transcriptomic and clinical data were downloaded from TCGA database, and ferroptosis-related genes were obtained from the FerrDb database. Through correlation analysis, Cox analysis, and the Lasso algorithm, 10 prognostic ferroptosis-related lncRNAs (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) were screened to construct a prognostic model, which was verified in two test cohorts. Risk scores for patients with stomach cancer were calculated, and patients were divided into two risk groups. The low-risk group, based on the median value, had a longer overall survival time in the KM curve, and a lower proportion of dead patients in the survival distribution curve. Potential mechanisms and possible functions were revealed using GSEA and the ceRNA network. By integrating clinical information, the association between lncRNAs and clinical features was analyzed and several features affecting prognosis were identified. Then, a nomogram was developed to predict survival rates, and its good predictive performance was indicated by a relatively high C-index (0.67118161) and a good match in calibration curves. Next, the association between these lncRNAs and therapy was explored. Patients in the low-risk group had an immune-activating environment, higher immune scores, higher TMB, lower TIDE scores, and higher expression of immune checkpoints, suggesting they might receive a greater benefit from immune checkpoint inhibitor therapy. In addition, a significant difference in the sensitivity to mitomycin. C, cisplatin, and docetaxel, but not etoposide and paclitaxel, was observed. In summary, this model had guiding significance for prognosis and personalized therapy. It helped screen patients with stomach cancer who might benefit from immunotherapy and guided the selection of personalized chemotherapeutic drugs.

Identification and validation of a novel cellular senescence-related lncRNA prognostic signature for predicting immunotherapy response in stomach adenocarcinoma

“…However, there is no relevant research on ADAMTS9-AS1 in STAD. Lai et al (2021) demonstrated that AL121748.1 was a ferroptosis-related lncRNA associated with immunotherapy responses in STAD patients. LINC00460 may play oncogenic roles and serve as a potential prognostic biomarker in various tumors ( Dai et al, 2020 ), including colorectal cancer, gastric cancer, head and neck squamous cell carcinoma, and hepatocellular carcinoma ( Jiang et al, 2019 ; Tu et al, 2019 ; Yang et al, 2020 ; Hou et al, 2021 ).…”

Immunological and prognostic analysis of PSENEN in low-grade gliomas: An immune infiltration-related prognostic biomarker

“…The most used predictive biomarkers for ICI are PD-L1, MSI, and TMB ( Wang Y. et al, 2021 ; Lai et al, 2022 ). In addition, a high tumor stemness index is associated with reduced PD-L1 expression in most cancers ( Malta et al, 2018 ).…”

Hub Genes, Diagnostic Model, and Predicted Drugs Related to Iron Metabolism in Alzheimer's Disease

“…Afterward, logistic regression was used to fit the relationship between these significant factors and the response variable. Finally, the diagnostic efficacy of the model was evaluated using receiver operating characteristic curves (ROCs) and the area under the ROC curve (Coat et al, 2015 ; Lai et al, 2021 ). These analyses were performed with the “stats” and “pROC” packages in R software.…”