Citing increasing evidence that alternative splicing (AS) events are common in cancer and are closely related to the tumor microenvironment (TME), researchers examined the prognostic value of AS events in patients with bladder cancer (BLCA). Their report, published in Heliyon, suggested a potential role of AS events in “the prognosis, [tumor immune microenvironment (TIME)], and immunotherapy of BLCA.”

The study’s authors, led by Xinyun Li, utilized clinical, transcriptome, and AS event data of patients with BLCA from the Cancer Genome Atlas Project database. A prognostic profile was developed with Cox and LASSO regression models, and the profile was then validated based on the dataset’s “clinical survival status, clinicopathologic features, tumor immune microenvironment (TIME), and immune checkpoint.” Li and colleagues also screened the AS-related genes with the greatest difference in expression between tumor and normal samples and established “the regulatory network of AS-splicing factors (SFs)… to unravel the potential regulatory mechanism of AS events in BLCA. “

According to the report, the BLCA prognostic signature was constructed based on seven AS events, and the predictive value of the signature was verified from multiple perspectives. The investigators highlighted that there was significant abnormal expression of PTGER3, an AS event-related gene, “the expression of which was associated with the survival, clinicopathological features, TIME, and immunotherapy of BLCA, suggesting that it has potential clinical application value.”

In closing, the study’s authors also noted that splicing factors PRPF39, LUC7L, HSPA8, and DDX21, could also potentially be biomarkers in BLCA. Ultimately, they suggested that their investigation “yielded new insights into the molecular mechanisms of and personalized immunotherapy for BLCA.”

Source: https://www.cell.com/heliyon/fulltext/S2405-8440(22)00282-1?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844022002821%3Fshowall%3Dtrue