Liver metastases are the most common cause of cancer-related deaths in colorectal cancer. Researchers at the Comprehensive Cancer Center (CCC) of the Medical University of Vienna have now succeeded for the first time in identifying certain short RNA segments – known as tRNA fragments – that can reliably predict which patients have a favourable or unfavourable prognosis. These tRNA fragments originate either from the cell nucleus or from the mitochondria of the tumour cells and have surprisingly contrasting prognostic effects.
"For the first time, we have been able to show that genomic RNA fragments predominantly indicate a poor prognosis, while mitochondrial fragments tend to have a protective role," explain Johannes Längle and Dietmar Pils from the Clinical Department of Visceral Surgery at the CCC of MedUni Vienna and Vienna General Hospital. The study has now been published in the leading journal "Journal of Translational Medicine" (IF 7.5).
tRNA fragments as reliable biomarkers
The team analysed tumour samples from patients with colorectal liver metastases (CRLM) who underwent surgery at the Department of General Surgery at MedUni Vienna. Using state-of-the-art sequencing methods (small RNA sequencing), different RNA fragments were identified. tRNA fragments (tRFs) are short sections that originate from so-called transport RNAs (tRNAs) and perform important regulatory functions in cells. These molecules regulate cell growth, stress response and immune reactions, among other things, and appear to play a key role in the development of cancer and metastases. The results clearly show that genomic fragments were associated with a poor prognosis in 94% of cases, while mitochondrial fragments signalled a more favourable prognosis in about a quarter of cases (26%).
Decisive step towards personalised cancer therapy
"These fragments could serve as prognostic markers in the future to identify patients at higher risk of an unfavourable outcome at an early stage," emphasises first author Rebecca Zirnbauer. She adds that it is particularly promising that the prognostic significance of the tRNA fragments was independent of already established clinical parameters.
Key role of mitochondrial tRNA networks
"Network analyses also showed that mitochondrial RNA fragments correlate particularly strongly with each other and form well-connected clusters. In follow-up studies, we want to investigate the biological mechanisms behind this strong connectivity and whether they are associated with the observed favourable prognostic effects," said the research team.
Publication: Journal of Translational Medicine
Differential prognostic roles and clinical implications of mitochondrial and genomic tRNA-derived fragments in colorectal liver metastases.
Zirnbauer R, Ammon D, Renner A, Hartman N, Kalinina P, Starlinger P, Stremitzer S, Schwarz C, Kaczirek K, Bergmann M, Pils D, Laengle J.
https://doi.org/10.1186/s12967-025-06850-3