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. 2021 Feb 26;12(2):220. doi: 10.1038/s41419-021-03511-3

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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. 1 — a CT scans of different disease stages from a ccRCC patient: sunitinib sensitive stage, one month after radical nephrectomy, new metastatic lesions occurred in left lymph node by 4 years’ sunitinib treatment (from left to right). b Heat map of TMT proteomics from cancer tissues from different disease stages. c GO functional annotation analyzed the up-regulated proteins and the most differentially expressed proteins were enriched in the lysosome. d GO functional annotation analyzed the down-regulated proteins and the most differentially expressed proteins were enriched in CAMS, ECM receptor interaction, and focal adhesion. e Representative images of hematoxylin-eosin (H&E) staining and TFE3 staining by immunohistochemical (IHC) in sunitinib sensitive tissues and sunitinib resistant tissues. Scale bar, 100 μm and 400 μm. f Representative TEM images of lysosome (red dotted circle) in sunitinib sensitive tissues and sunitinib resistant tissues Scale bar 50 μm. Higher magnification insets showed the autophagosome (yellow) was engulfing the ER fragment (blue) in sunitinib-resistant tissues compared with sunitinib-sensitive tissues. Scale bar 5 μm.