Document Type

Article

Publication Date

9-16-2026

Comments

This article is the author’s final published version in Oncology reports, Volume 56, Issue 5, 2026.

The published version is available at https://doi.org/10.3892/or.2026.9196. Copyright © 2026 Zezulinski et al.

 

Abstract

Liquid biopsy can transform oncology practice through early detection and real‑time monitoring of cancer progression and response to treatment. Circulating cell‑free tumor RNA offers promise as a novel and emerging alternative to circulating cell‑free tumor DNA for detecting the presence and understanding the biology of liver tumors. Both circulating DNA and RNA, which predominantly reside in extracellular vesicles, carry evidence of vital germline and somatic mutations. High impact single nucleotide changes, insertions and deletions in circulating RNA (ctRNA) serve a key role in cancer development and progression. Tumor cells exploit the RNA splicing machinery to induce structural and functional changes in RNA not transcribed from DNA, thereby promoting tumor growth. Examination of the landscape of mutations in ctRNA using RNA‑sequencing in patients with hepatocellular carcinoma (HCC), cholangiocarcinoma and liver cirrhosis has revealed widespread single nucleotide changes and splicing aberrations associated with patients with cancer. The present study aimed to characterize these next‑generation sequencing‑derived high‑risk circulating mutated RNA (ctmutRNA) variants, and to develop TaqMan chemistry‑based assays for validation of ctmutRNAs in tumor tissues and plasma samples from patients with HCC. The present study identified a short ctmutRNA panel able to distinguish all patients with liver cancer in the discovery cohort, and splicing aberrations, including intron retentions, in tumor tissues were validated. Finally, the present study demonstrated that the assays detecting ctmutRNA analytes in the plasma, if confirmed in larger patient cohorts, could be effectively used to identify patients with HCC. Furthermore, the outstanding questions and challenges that need to be addressed for the development of a robust blood‑based HCC surveillance test are discussed.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Language

English

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