Construction of a disulfidptosis-associated lncRNA signature to predict prognosis in bladder cancer.

Abstract

Background: Bladder cancer (BCa) is the most common neoplasm of the urinary system, and its high rates of progression and recurrence contribute to a generally poor prognosis, especially in advanced cases. It is reported that disulfidptosis is closely related with tumor proliferation. We aimed to construct a disulfidptosis-associated long non-coding RNA (lncRNA) signature that can predict prognosis and immune microenvironment in BCa.

Methods: We obtained RNA-seq data, clinical information, and mutation data of BCa patients from The Cancer Genome Atlas (TCGA) database. Based on Pearson correlation and uni-Cox regression analysis, we identified disulfidptosis-associated lncRNAs related with overall survival (OS). Then a prognosis signature based on seven disulfidptosis-associated lncRNAs was constructed by least absolute shrinkage and selection operator (LASSO) Cox regression analysis and multi-Cox regression analysis. We performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) analyses to examine biological functional of differentially expressed genes related to the risk model. We assessed the immune microenvironment and chemotherapeutic response of several drugs. Finally, the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression level of the disulfidptosis-associated lncRNAs.

Results: We established a prognosis signature based on seven disulfidptosis-associated lncRNAs (AP003419.3, AL161891.1, AC234917.3, LINC00536, AL021707.6, AL445649.1 and AC104785.1). According to the signature, all patients were divided in high- and low-risk group and patients in low-risk group showed a significantly better prognosis. Moreover, the risk model was confirmed to be an independent prognostic factor with high accuracy. Immune cells and several immune checkpoints were more active in high-risk group and patients in this group had a higher tumor mutation burden (TMB) that those in low-risk group. The results of qRT-PCR demonstrated that expression level of the lncRNAs were all significantly different between BCa cell lines and normal urinary epithelial cells.

Conclusions: The disulfidptosis-associated lncRNA signature is a promising biomarker for predicting prognosis and characterizing the immune landscape in BCa, potentially guiding personalized treatment strategies.