Unlocking the Potential of Disulfidptosis‐Related LncRNAs in Lung Adenocarcinoma: A Promising Prognostic LncRNA Model for Survival and Immunotherapy Prediction

• Published in: Cancer medicine (Malden, MA) MA), 2024-10, Vol.13 (20), p.e70337-n/a
• Main Authors: Nie, Xin, Ge, Hong, Wu, Kongming, Liu, Ru, He, Chunyu
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Adenocarcinoma of Lung - genetics; Adenocarcinoma of Lung - immunology; Adenocarcinoma of Lung - mortality; Adenocarcinoma of Lung - pathology; Adenocarcinoma of Lung - therapy; Biomarkers, Tumor - genetics; Cancer therapies; Cell cycle; Cell migration; Cell survival; Chemotherapy; CIBERSORT; Databases, Genetic; disulfidptosis; ESTIMATE; Gene Expression Regulation, Neoplastic; Genes; Genomics; Glucose; Humans; Immune checkpoint inhibitors; Immunoglobulin A; Immunotherapy; Immunotherapy - methods; lncRNA; lung adenocarcinoma; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - therapy; Medical prognosis; Nomograms; Non-coding RNA; Predictions; Principal components analysis; Prognosis; RNA, Long Noncoding - genetics; TMB; Tumor microenvironment; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.70337

ABSTRACT Objective Disulfidptosis was stimulated in high SLC7A11 expression cells starving to glucose. We attempted to identify disulfidptosis‐related lncRNAs (DRLs), built a prognostic model to predict survival, and analyzed the tumor microenvironment. Methods The TCGA database was utilized to procure the pertinent data. By utilizing both Cox regression and the least absolute shrinkage and selection operator (LASSO) method, a risk model based on DRLs was formulated for prognostic evaluation. The ability of survival prediction was validated by multiple approaches. The biological functions were screened through GO, KEGG, and GSEA. Various methods were employed to evaluate the tumor immune environment, which included ESTIMATE, tumor mutation burden (TMB) score, CIBERSORT algorithm, and tumor immune dysfunction and exclusion (TIDE) score. Results Ninety‐one DRLs were recognized, and lncRNA AC092718.4, AL365181.2, AL606489.1, EMSLR, and ENTPD3‐AS1 were involved in the risk model. The GEO database was used to verify the influence of these lncRNAs on survival. The following analyses showed that survival could be predicted excellently by the DRLs risk model. The results of enrichment analyses pointed toward the involvement of the cell cycle and IgA production pathways. In the low‐risk patient group, there was a notable surge in stromal, immune, and ESTIMATE scores, while the TMB scores took a tumble. Conversely, the high‐risk patient group displayed a converse trend. Notably, the group of patients with lower risk scores and higher TMB scores showed the most favorable survival outcomes, underscoring the importance of considering both risk score and TMB in predicting the response to immune checkpoint blockade therapy. Furthermore, patients classified as high‐risk might display resistance to both chemotherapy and targeted therapy. Cellular biological experiments proved that lncRNA AC092718.4 promoted invasion, migration, and proliferation abilities in vitro. These results provided valuable insights into the role of DRLs in LUAD and presented a possible effective treatment approach for LUAD. Conclusions We developed a disulfidptosis‐related risk model with 5 lncRNAs that enables survival prediciton for LUAD patients and aids cilinical decisions by forecasting the TME, TMB, and drug sensitivity, making it a valuable tool for outcomes prediction.