Abstract Background: Formalin-fixed, paraffin-embedded (FFPE) tissues remain essential resources for cancer research and the discovery of clinically relevant biomarkers. However, RNA extracted from FFPE samples is often highly degraded, chemically modified, and fragmented, posing major challenges for transcriptomic analyses, including gene expression profiling and RNA fusion detection. To address the need for a robust RNA-seq method capable of handling severely degraded RNA, we developed the PredicineWTS Tissue platform, which integrates optimized extraction chemistry with a proprietary RNA-seq pipeline tailored for FFPE RNA. Methods: The PredicineWTS Tissue platform employs a proprietary extraction protocol that simultaneously isolates DNA and RNA from a single FFPE section, maximizing material utility for multi-omics applications. The RNA-seq workflow supports inputs as low as 10 ng and tolerates extreme degradation, including DV200 values down to 10%. A customized bioinformatics pipeline enables comprehensive expression profiling and detection of RNA fusions and splicing variants. DNA isolated during extraction is preserved for downstream genomic assays, enabling integrated analyses. Performance validation was performed using commercial reference materials. Results: The platform showed strong performance on heavily degraded FFPE RNA. High-quality libraries were generated from samples with DV200 values as low as 10%, achieving approximately 93% uniquely mapped reads, 90% exonic reads, and detection of ∼19,000 genes. Expression accuracy correlated strongly with an independent third-party company’s results (Pearson r ≥ 0.94). Fusion detection sensitivity was evaluated using titrated Seraseq material (50%, 20%, 10%, and 5% tumor purity), and all expected fusions were detected down to the 10% tumor purity, supporting sensitivity for low-abundance events relevant to cancer biomarker discovery. DNA recovered during extraction showed yield and quality comparable to leading extraction methods, further supporting workflow versatility. Conclusion: PredicineWTS Tissue assay provides a powerful and reliable RNA-seq solution of severely degraded FFPE samples. By enabling robust expression profiling and sensitive fusion detection at low RNA quality and input, the platform advances biomarker discovery and supports integrated multi-omics studies. Its performance with archival and challenging FFPE material positions it as a valuable technology for precision oncology and translational research. Citation Format: Min Wang, Yasser Abdelrahman, Guanglong Jiang, Yong Huang, Pan Du, Binggang Xiang. A robust RNA-seq solution for severely degraded FFPE samples: The PredicineWTS Tissue NGS platform abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3818.
Wang et al. (Fri,) studied this question.