%0 Journal Article
%T A Novel Eight-lncRNA Disulfidptosis Signature Stratifies Prognosis and Immunotherapeutic Benefit in LUAD
%A Thandeka Moyo
%A Sipho Dlamini
%A Kabelo Ndlovu
%J Specialty Journal of Pharmacognosy, Phytochemistry, and Biotechnology
%@ 3062-441X
%D 2024
%V 4
%N 1
%R 10.51847/ynKIf1yzPT
%P 104-117
%X Lung adenocarcinoma (LUAD), the predominant form of lung malignancy, is associated with unfavorable clinical outcomes. Disulfidptosis, a recently described programmed cell-death mechanism, arises from excessive disulfide accumulation and disruption of the actin cytoskeleton. This work sought to pinpoint lncRNAs linked to disulfidptosis and to construct a disulfidptosis-associated lncRNA signature capable of forecasting LUAD prognosis and therapeutic responsiveness. RNA-seq profiles and clinical characteristics for LUAD cases were extracted from the TCGA database. Disulfidptosis-related lncRNAs connected to overall survival were screened through Pearson correlation together with Cox regression. A prognostic signature was produced via LASSO analysis. GO, KEGG, and GSEA functional annotations were applied to determine biological pathways enriched in the model. Immune infiltration was quantified using ESTIMATE and CIBERSORT. Simple nucleotide variation data were utilized to evaluate tumor mutational burden (TMB) and its relationship to the risk score. Patients’ sensitivity to immunotherapy and antitumor agents was estimated via the TIDE algorithm and the GDSC platform.
A total of 127 lncRNAs associated with disulfidptosis were identified, and a prognostic panel containing eight of them (KTN1-AS1, AL365181.3, MANCR, LINC01352, AC090559.1, AC093673.1, AP001094.3, MHENCR) was constructed and validated. This model separated LUAD individuals into two distinct risk categories. Elevated risk scores independently predicted unfavorable overall survival and were linked to diminished immune infiltration, increased TMB, and weaker antitumor immune activation. High-risk cases were more likely to derive benefit from immune checkpoint blockade, whereas low-risk counterparts showed higher predicted responsiveness to targeted agents and multiple kinase inhibitors. We developed a disulfidptosis-associated lncRNA signature that may aid in forecasting survival, mutation burden, immune infiltration patterns, and likely responses to immunotherapy and targeted treatment in LUAD.
%U https://galaxypub.co/article/a-novel-eight-lncrna-disulfidptosis-signature-stratifies-prognosis-and-immunotherapeutic-benefit-in-8dgsot4940wdy3u