Identification of Immune-Related lncRNA Signature to Predict Prognosis and Immunotherapeutic Efficiency in Bladder Cancer

Purpose: Identify immune-related lncRNA (IRL) signature related to the prognosis and immunotherapeutic efficiency for bladder cancer (BLCA) patients.

Methods: A total of 397 samples, which contained RNA-seq and clinical information from The Cancer Genome Atlas (TCGA) database, were used for the following study. Then the Lasso penalized Cox proportional hazards regression model was used to construct prognostic signature. According to the optimal cut-off value determined by time-dependent ROC curve, low and high-risk groups were set up. One immunotherapy microarray dataset as validation set was used to verify the ability of predicting immunotherapy efficacy. Furthermore, more evaluation between two risk groups related clinical factors were conducted. Finally, external validation of IRL-signature was conducted in Zhengzhou cohort.

Result: Four IRLs (HCP5, IPO5P1, LINC00942, and LINC01356) with significant prognostic value (P<0.05) were distinguished. This signature can accurately predict the overall survival of BLCA patients and was verified in the immunotherapy validation set. IRL-signatures can be used as independent prognostic risk factor in various clinical subgroups. According to the results of GSVA and MCP algorithm, we found that IRL-signature risk score is strikingly negative correlated with tumor microenvironment (TME) CD8+T cells and Cytotoxic lymphocytes infiltration, indicating that the better prognosis and immunotherapy might be caused partly by these. Then, the results from the TIDE analysis revealed that IRL could efficiently predict the response of immunotherapy in BLCA. External validation had similar results with TCGA-BLCA cohort.

Conclusions: The novel IRL-signature has a significant prognostic value for BLCA patients might facilitate predicting the efficacy of immunotherapy.