Authors
Nada Humayun-Zakaria, Minghao Yu, Anshita Goel, Naheema S Gordon, Stuart Savill, Andrew S Mason, Maurice P Zeegers, K K Cheng, Nicholas D James, Douglas G Ward, Richard T Bryan, Roland Arnold
Published in
Scientific reports. Volume 16. Pages 37672. Epub Oct 17, 2026.
Abstract
mRNA isoform level-based biomarkers are understudied but might complement DNA based approaches. The expression of tropomyosin isoforms differs between normal and cancer cells. Tropomyosin (TPM) isoforms generated by alternative splicing may contribute to Bladder Cancer (BC) biology, but their diagnostic potential has not been defined. We analysed RNAseq data from six independent BC datasets to predict TPM isoform expression. Predictions were validated through targeted long-read sequencing and isoform-specific quantitative PCR (qPCR) in archived tumour tissues (n = 90) and BC cell lines (n = 5). Urine samples from patients with BC (n = 12) and non-cancer controls (n = 16) were assessed for diagnostic performance. The expression ratios of 2 pairs of isoforms Tpm1.7/Tpm1.4 and Tpm4.2/Tpm4.1 were 2.4- and 1.4- fold higher in BC compared with non-BC tissues (p-value = 0.0003, 0.0005, respectively). In urine specimens, the ratio of Tpm4.2/Tpm4.1 was 2.66 times higher in cancer vs controls (p = 0.0031) and achieved 92% sensitivity and 69% specificity for BC detection. TPM isoform switching events are associated with bladder carcinogenesis. Assessment of TPM isoform expression by a non-invasive urine-based qPCR assay shows promise for BC detection and may complement existing diagnostic strategies.
The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-66033-y.
PMID:
43024385
Bibliographic data and abstract were imported from PubMed on 14 Nov 2026.
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