AUTHOR=Mo Xiaocong , Hu Di , Li Yin , Nai Aitao , Ma Feng , Bashir Shoaib , Jia Guoxia , Xu Meng 

TITLE=A novel pyroptosis-related prognostic lncRNAs signature, tumor immune microenvironment and the associated regulation axes in bladder cancer

JOURNAL=Frontiers in Genetics

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.936305

DOI=10.3389/fgene.2022.936305

ISSN=1664-8021

ABSTRACT=Pyroptosis is a newly identified programmed cell death which could regulate tumor cell proliferation and progression. Long non-coding RNAs (LncRNAs) are key mole-cules and potential biomarkers for diagnosing and treating various diseases. However, the effects of pyroptosis-related LncRNAs (PRLs) on bladder cancer (BC) have not yet been completely elucidated. In our study, a prognostic PRLs model and two ceRNA networks were established using sufficient bioinformatics analysis and pre-liminary RT-qPCR validation in vitro. We found a strong correlation between PRLs and tumor immune microenvironment by Pearson's correlation analysis. 6 PRLs were selected to establish a prognostic model using univariate Cox regression analysis, LASSO algorithm, and multivariate analysis. Then, the prognostic model was proved to be an effective independent factor compared with other clinical features by Cox regression analyses (Training cohort: Univariate analysis: HR=1.786, 95% Cl = 1.416-2.252, P<0.001; multivariate analysis: HR=1.664, 95% Cl = 1.308-2.116, P<0.001; testing cohort: Univariate analysis: HR=1.268, 95% Cl = 1.144-1.405, P<0.001; multivariate analysis: HR=1.141, 95% Cl = 1.018-1.280, P=0.024). In ad-dition, both analyses (ROC and nomogram) were used to corroborate the accuracy and reliability of this signature (1-year-AUC=0.764, 3-year-AUC=0.769, 5-year-AUC=0.738). Consequently, we evaluated the survival curves of these 6 lncRNAs using Kaplan–Meier survival analysis, demonstrating that MAFG-DT was risk lncRNA, while OCIAD1-AS1, SLC25A25-AS1, SNHG18, PSMB8-AS1 and TRM31-AS1 were protective lncRNAs. The correlation between PRLs and immune infiltra-tion was elucidated, finding that the degrees of infiltration of 6 immune cells and 14 immune-correlated pathways were differed significantly in the two risk groups. As for sensitivity of anti-tumor drugs, the high-risk group was more sensitive to Soraf-enib, Bicalutamide and Cisplatin, while the low-risk group was more sensitive to AKT.inhibitor.VIII, salubrinal and Lenalidomide, etc. Furthermore, our results also identified lncRNA OCIAD1-AS1/miR-141-3p/GPM6B and lncRNA OCIAD1-AS1/ miR-200a-3p/AKAP11 regulatory axes, which may play a potential role in the pro-gression of BC.