Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

Zhenyu Wu; Yue Wang; Mengxin Yan; Quan Liang; Bin Li; Guoliang Hou; Taolin Xia; Zhe Lin; Wenfeng Xu

doi:10.3389/fonc.2022.951631

Comprehensive analysis of the endoplasmic reticulum stress-related long non-coding RNA in bladder cancer

Front Oncol. 2022 Aug 4:12:951631. doi: 10.3389/fonc.2022.951631. eCollection 2022.

Authors

Zhenyu Wu¹, Yue Wang², Mengxin Yan², Quan Liang¹, Bin Li¹, Guoliang Hou¹, Taolin Xia¹, Zhe Lin¹, Wenfeng Xu¹

Affiliations

¹ Department of Urology, The First People's Hospital of Foshan, Foshan, China.
² The First Clinical Medical College, GuangDong Medical University, ZhanJiang, China.

Abstract

Background: Bladder cancer is ranked the second most frequent tumor among urological malignancies. The research strived to establish a prognostic model based on endoplasmic reticulum stress (ERS)-related long non-coding RNA (lncRNA) in bladder cancer.

Methods: We extracted the ERS-related genes from the published research and bladder cancer data from the Cancer Genome Atlas database. ERS-related lncRNAs with prognostic significance were screened by univariate Cox regression, least absolute shrinkage and selection operator regression analysis and Kaplan-Meier method. Multivariate Cox analysis was leveraged to establish the risk score model. Moreover, an independent dataset, GSE31684, was used to validate the model's efficacy. The nomogram was constructed based on the risk score and clinical variables. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the ERS-related signature. Finally, we employed external datasets (GSE55433 and GSE89006) and qRT-PCR to investigate the expression profile of these lncRNAs in bladder cancer tissues and cells.

Results: Six ERS-related lncRNAs were identified to be closely coupled with patients' prognosis. On this foundation, a risk score model was created to generate the risk score for each patient. The ERS-related risk score was shown to be an independent prognostic factor. And the results of GSE31684 dataset also supported this conclusion. Then, a nomogram was constructed based on risk scores and clinical characteristics, and proven to have excellent predictive value. Moreover, the gene function analysis demonstrated that ERS-related lncRNAs were closely linked to fatty extracellular matrix, cytokines, cell adhesion, and tumor pathways. Further analysis revealed the association of the 6-lncRNAs signature with gene mutations and immunity in bladder cancer. Finally, the external datasets and qRT-PCR verified high expressions of the ERS-related lncRNAs in bladder cancer tissues and cells.

Conclusions: Overall, our findings indicated that ERS-related lncRNAs, which may affect tumor pathogenesis in a number of ways, might be exploited to assess the prognosis of bladder cancer patients.

Keywords: ERS; TCGA; bladder cancer; lncRNA; prognostic model.