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Open Access 18-07-2022 | Metastasis | Original Article

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

Authors: 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

Published in: Cellular Oncology | Issue 4/2022

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

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Title: EV-miRome-wide profiling uncovers miR-320c for detecting metastatic colorectal cancer and monitoring the therapeutic response
Authors: 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
Publication date: 18-07-2022
Publisher: Springer Netherlands
Keywords: Metastasis
Colorectal Cancer
Colorectal Cancer
Published in: Cellular Oncology / Issue 4/2022
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI: https://doi.org/10.1007/s13402-022-00688-3

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