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Detection of circulating microRNAs with Ago2 complexes to monitor the tumor dynamics of colorectal cancer patients during chemotherapy
Author(s) -
Fuji Tomokazu,
Umeda Yuzo,
Nyuya Akihiro,
Taniguchi Fumitaka,
Kawai Takashi,
Yasui Kazuya,
Toshima Toshiaki,
Yoshida Kazuhiro,
Fujiwara Toshiyoshi,
Goel Ajay,
Nagasaka Takeshi
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.31960
Subject(s) - microrna , colorectal cancer , biomarker , cytolysis , metastasis , chemotherapy , cancer , cancer research , extracellular , medicine , biology , in vitro , cytotoxicity , gene , microbiology and biotechnology , biochemistry
Because of the different forms of circulating miRNAs in plasma, Argonaute2 (Ago2)‐miRNAs and extracellular vesicles (EV‐miRNAs), we examined the two forms of extracellular miRNAs in vitro and developed a unique methodology to detect circulating Ago2‐miRNAs in small volumes of plasma. We demonstrated that Ago2‐ miR‐21 could be released into the extracellular fluid by active export from viable cancer cells and cytolysis in vitro . As miR‐21 and miR‐200c were abundantly expressed in both metastatic liver sites and primary lesions, we evaluated Ago2‐ miR‐21 as a candidate biomarker of both active export and cytolysis while Ago2‐ miR‐200c as a biomarker of cytolysis in plasma obtained from colorectal cancer (CRC) patients before treatment and in a series of plasma obtained from CRC patients with liver metastasis who received systemic chemotherapy. The measurement of Ago2 ‐miR‐21 allowed us to distinguish CRC patients from subjects without CRC. The trend in ΔCt values for Ago2 ‐miR‐21 and ‐200c during chemotherapy could predict tumor response to ongoing treatment. Thus, capturing circulating Ago2‐miRNAs from active export can screen patients with tumor burdens, while capturing them from passive release by cytolysis can monitor tumor dynamics during chemotherapy treatment.