EV-miRome-wide profiling uncovers miR-320c for detecting metastatic colorectal cancer and monitoring the therapeutic response

Chan-Keng Yang, Hung Chih Hsu, Yu Hao Liu, Wen Sy Tsai, Chung Pei Ma, Yi Tung Chen, Bertrand Chin Ming Tan, Ying Yu Lai, Ian Yi Feng Chang, Chi Yang, Chia Yu Yang, Jau Song Yu, Hsuan Liu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

9 Scopus citations

Abstract

Purpose: Molecular composition of circulating small extracellular vesicles (EVs) does not merely reflect the cells of origin, but also is enriched in specific biomolecules directly associated with the cellular transformation. However, while most of the currently identified EV-miRs are only geared towards one-dimensional disease detection, their application for long-term tracking and treatment response monitoring has been largely elusive. Methods: We established and optimized a rapid, sensitive and robust liquid biopsy sampling method, and further used small RNA sequencing to comprehensively catalogue EV-miRomes in association with the progression and outcome of metastatic colorectal cancer (mCRC). Results: By cross-comparison of EV-miRomes (n = 290) from multi-stage and longitudinal cohorts, we uncovered a 15-EV-miR signature with dual detection and long-term monitoring of tumor size progression for mCRC. From this panel, EV-miR-320c was uncovered as a strong clinical marker – aside from its diagnostic power and a therapeutic monitoring performance superior to carcinoembryonic antigen (CEA), its high expression has also been linked to lower overall survival and a greater likelihood of disease recurrence. Further, integrative analyses of tissue transcriptomic and liquid biopsy implicated this 15-EV-miR signature in programming the mesenchymal–epithelial transition (MET) for distant localization of the metastasized cells and also in creating a tumor-favoring metastatic niche. Conclusion: Our clinically-oriented delineation of the mCRC-associated circulating EV-miRomes systematically revealed the functional significance of these liquid biopsy markers and further strengthen their translational potential in mCRC therapeutic monitoring. Graphical abstract: [Figure not available: see fulltext.]

Original languageEnglish
Pages (from-to)621-638
Number of pages18
JournalCellular Oncology
Volume45
Issue number4
DOIs
StatePublished - 08 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Keywords

  • Mesenchymal–epithelial transition
  • Metastasis colorectal cancer
  • Small RNA sequencing
  • Small extracellular vesicles
  • miRome

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