Exosomal miRNAs as circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.J Cell Mol Med. 2020 06; 24(11):6220-6232.JC
Exosomes secreted by living cancer cells can regulate metastasis. Exosomal miRNAs can reflect pathological conditions of the original cancer cells. Therefore, we aim to identify exosomal miRNAs as circulating biomarkers for haematogenous metastasis of gastric cancer. Pre-treatment serum samples of eighty-nine patients with stage II/III gastric cancer were collected. Thirty-four of them developed haematogenous metastasis after surgery and the other fifty-five did not. Extraction of exosomes was validated by western blot, transmission electron microscopy and nanoparticle tracking analysis. MiRNA qPCR array was performed in three matched pairs of samples. Internal control was selected from PCR array and validated in the remaining samples. Expressions of exosomal miRNAs were evaluated in the remaining samples by RT-qPCR, as well as in gastric cancer tissue samples and cell culture medium. Expression levels of exosomal miRNAs were analysed with clinical characteristics. The results indicated thirteen up-regulated and six down-regulated miRNAs were found after normalization. MiR-379-5p and miR-410-3p were significantly up-regulated in metastatic patients (P < .01). Higher expression of exosomal miR-379-5p or miR-410-3p showed shorter progression-free survival of the patients (P < .05). It was also found that miR-379-5p and miR-410-3p were down-regulated in gastric cancer tissue samples, while they were significantly up-regulated in gastric cancer cell culture medium compared with cancer cells. In conclusion, exosomal miRNAs are promising circulating biomarkers for prediction of development of haematogenous metastasis after surgery for stage II/III gastric cancer.