A Prognostic Necroptosis-Related lncRNA Signature to Predict the Immune Response and Drug Sensitivity of Bladder Cancer

Background: Patients with bladder cancer (BLCA), especially those with advanced stage cancer, have a short life span; thus, new drugs need to be developed urgently to improve the situation. Long noncoding RNAs (lncRNAs) are considered regulatory targets for cancer, including BLCA. Therefore, we constructed a promising signature of lncRNAs related to necroptosis and further predicted the immune response and sensitivity of drugs. Methods: : We downloaded the transcriptome and clinical data for BLCA from the Cancer Genome Atlas（TCGA）. Necroptosis related to lncRNAs (nrlncRNAs) was subsequently identified by univariate Cox regression. We then constructed the signature by performing the least absolute shrinkage and selection operator(LASSO) and evaluated it by Kaplan–Meier analysis, multivariate Cox regression, time-dependent receiver operating characteristics (ROC), nomogram, calibration curves, gene set enrichment analyses(GSEA), immune checkpoint, tumor microenvironment(TME), N6-methyladenosine (m6A) modification genes, and the half-maximal inhibitory concentration (IC50) analysis in the risk groups. Results: : An 11-nrlncRNAs (AC008750.1, AL133297.1, AC005479.1, AP003559.1, UBE2Q1-AS1, MIR100HG, LINC02709, AC005387.1, LINC00649, AC021321.1, ETV7-AS1) prognostic signature was constructed. Immune checkpoint analysis revealed that the expression of most of the immune genes in the high-risk group was higher than those in the low-risk group. The signature predicted different IC50 values to have statistical significance in high-and low-risk groups for multiple drugs. Conclusion: Our constructed signature may contribute to the prognosis of patients with BLCA as well as serve as clinical predictors of chemotherapy and immunotherapy.