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. 2021 Jan 4;22:4. doi: 10.1186/s13059-020-02222-w

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© The Author(s) 2021

Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

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Fig. 4 — Reversed EMT and metabolism rewiring in HMs. a Compared to PT, HMs showed decreased activities of EMT and EMT related pathways (upper panel) as well as increased cell cycle activity (bottom panel). This phenomenon was experimentally validated by IFH assays of 35 paired PTs and HMs. b HMs showed significant upregulation of epithelial marker E-cadherin and downregulation of mesenchymal marker N-cadherin. c TGFβ1 and WNT5A that are ligands of TGFβ signaling and WNT signaling, respectively, were significantly upregulated in HMs. d Proliferative marker Ki67 and CCNA2 were upregulated in HMs compare to PTs. *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001. e Oxidative phosphorylation, pentose phosphate pathway, and glycolysis were up-regulated in HMs. Top panel shows results of between-group comparisons. Bottom panel shows difference between HMs and PTs of individual cases. Green indicates up regulation while purple indicates down regulation in HM. f Gene expression heat-map of key components of pathways showed in e