Comprehensive long-read transcriptome analysis uncovers alternative RNA processing feature and isoform diversity in ovarian cancer progression

Liu, T.; Lv, J.; Wang, S.; Liu, Y.; Chen, Y.; Li, J.; Wang, L.; Shi, Y.; Li, N.; Ding, W.; Piao, Y.

doi:10.64898/2026.03.11.710989

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bioRxiv · 10.64898/2026.03.11.710989

Comprehensive long-read transcriptome analysis uncovers alternative RNA processing feature and isoform diversity in ovarian cancer progression

Liu, T.·Lv, J.·Wang, S.·Liu, Y.·Chen, Y.·Li, J.·Wang, L.·Shi, Y.·Li, N.·Ding, W.·Piao, Y.

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Abstract

Post-transcriptional processing has a crucial yet largely unresolved dynamic change and role during the malignant progression of ovarian cancer, especially due to the limited read length of short-read RNA sequencing being insufficient to capture transcript diversity. Here, we performed Iso and RNA sequencing on paired normal, primary tumor, and metastatic samples, generating a comprehensive isoform atlas of over 41,000 full-length transcripts including many unannotated isoforms. Integrative analyses revealed extensive isoform-level remodeling across disease states that often occurred without concordant alterations at the gene level, emphasizing the importance of qualitative transcript regulation. Notably, we identified isoform-level alterations with distinct biological and clinical relevance, including differential expression of the short KRAS isoform, a tumor-specific isoform switch of TMEM201, and an alternative first-exon event in FNDC3B associated with poor survival. Together, these findings provide a high-resolution map of the ovarian cancer transcriptome and illustrate how long-read sequencing exposes multiple layers of post-transcriptional and clinical insight that remain hidden in conventional expression profiling.

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Liu, T., Lv, J., Wang, S., Liu, Y., Chen, Y., Li, J., Wang, L., Shi, Y., Li, N., Ding, W., Piao, Y.. 2026-03-14. Comprehensive long-read transcriptome analysis uncovers alternative RNA processing feature and isoform diversity in ovarian cancer progression. https://doi.org/10.64898/2026.03.11.710989

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