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. 2021 May 26;6:187. doi: 10.1038/s41392-021-00579-3

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — Plasma exosomal S100A4 and OPN levels jointly serve as a powerful postoperative prognostic factor for HCC patients. a Working model of exosomal S100A4 promoting HCC metastasis. S100A4^rich exosomes released by highly metastatic HCC cells enhanced metastatic potential of low metastatic HCC cells via STAT3 phosphorylation and OPN up-regulation. b Correlation analysis on plasma OPN level and plasma exosomal level of S100A4 showed positive correlation in clinical samples. c, d Patients with low plasma exosomal S100A4 level had significantly better overall survival (OS) and time to treat (TTR) compared with HCC patients with high plasma exosomal S100A4 level. e, f Patients with both low plasma exosomal S100A4 level and OPN level had the longest OS and DFS among the four subgroups, which were divided according to combination of exosomal S100A4 and OPN. For each cohort, different subgroups were plotted according to the cut-off values of exosomal S100A4 (98.54 pg/ml) and OPN (103.78 ng/ml). Error bars represent the mean ± SD, and the dots represent the value of each experiment; *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, ns: no significance. Simple linear regression was employed in (b), log-rank test was employed in (c–f)