Immune-related long non-coding RNA signature identified prognosis and immunotherapeutic efficiency in bladder cancer (BLCA)

Bladder Cancer
01/07/2020

Cao R, et al. Cancer Cell Int 2020.

ABSTRACT

BACKGROUND: As bladder cancer was recognized to be immunogenic, dozens of studies have focused on immune biology of BLCA, but little is known about its relationship with the long non-coding RNAs (lncRNAs).

METHODS: LASSO Cox regression model was used to establish immune-related lncRNAs signature (IRLS) in BLCA. The immune infiltration landscape of BLCA was conducted via ssGSEA and immunotherapy response was calculated through TIDE algorithm.

RESULTS: A total of 82 immune-related lncRNAs were screened out according to spearman correlation analysis with the immune score (|R| > 0.4, p < 0.05). We selected 5 prognostic lncRNAs to construct immune-related lncRNAs signature (IRLS) through LASSO Cox regression analysis. Then we validated that 5 enrolled lncRNAs was downregulated in BLCA tissues and cells when compared with paracancerous tissues and normal bladder epithelium cell. The univariate and multivariate Cox regression analysis both demonstrated the IRLS was a robust independent prognostic factor in overall survival prediction with high accuracy. The GSVA and GSEA also suggested that the IRLS are involved in the immune-related biological processes and pathways which are very well known in the context of BLCA tumorigenesis. In addition, we found that IRLS is strikingly positive correlated with tumour microenvironment (TME) immune cells infiltration and expression of critical immune checkpoints, indicating that the poor prognosis might be caused partly by immunosuppressive TME. Finally, the results from the TIDE analysis revealed that IRLS could efficiently predict the clinical response of immunotherapy in BLCA.

CONCLUSION: We have developed a novel IRLS, which have a latent prognostic value for BLCA patients and might facilitate personalized counselling for immunotherapy.