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Thomas Flaig, MD


Can Alternative Splicing Help to Reveal a Prognostic Biomarker in Muscle-Invasive Bladder Cancer?

By: Victoria Kuhr, BA
Posted: Tuesday, October 4, 2022

Qichao Xie, MD, of The Third Affiliated Hospital of Chongqing Medical University, China, observed that a 15–alternative splicing events signature may serve as a prognostic biomarker for patients with muscle-invasive bladder cancer. Additionally, the prevalence of FGFR3-contained mutations and focal amplification suggests distinct signaling pathways and immune states between high- and low-risk patient groups. These findings were published in the World Journal of Surgical Oncology.

“[These] data revealed that one single gene harbored almost four alternative splicing events on average, which implied that the different arrangements and reconstructions of splicing types might play a vital role in the transcriptomic isoform diversity,” said the study authors.

Percent spliced in data from the Cancer Genome Atlas SpliceSeq database were used to evaluate alternative splicing in muscle-invasive bladder cancer. Patients were included in the study if they had completed clinicopathologic information and at least 30 days of overall survival.

A total of 394 patients with muscle-invasive bladder cancer were included in the study. Of them, 2,589 prognosis-related alternative splicing events from 1,732 parent genes were significantly associated with overall survival in muscle-invasive bladder cancer. These data accounted for 13.5% of all alternative splicing events and 24.8% of their parent genes in muscle-invasive bladder cancer. Gene ontology pathway analyses suggested that prognostic alternative splicing events may be mediated by RNA spliceosomal complex and DNA-directed RNA polymerase II. Of these events, pathways of spliceosomal, DNA-directed RNA polymerase II, core complex, and base excision repair were observed to be significantly enriched.

The study authors created a 15–alternative splicing prognostic events signature in training set. Patients with muscle-invasive bladder cancer were divided into high- and low-risk scores based on median risk scores. Patients in the high-risk group had significantly shorter overall survival and more often participated in several processes of stimulating tumor proliferation and metastasis.

Disclosures: The study authors reported no conflicts of interest.

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