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. 2022 Apr 19;13:2052. doi: 10.1038/s41467-022-29577-x

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© The Author(s) 2022

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. 4 — a PCA of 7,267 proteins in 232 paired tumor and adjacent tissue samples. Orange, tumor tissue; purple, tumor adjacent tissue. b Volcano plot showing DEPs (two-sided paired t test, Benjamini–Hochberg-adjusted p value < 0.01, FC > 2) in tumor and adjacent tissues. Proteins that were significantly overexpressed in tumor/adjacent tissues are presented with orange/purple filled scatters. c DEPs in tumors and adjacent tissues, and their associated biological pathways. d Dysregulation of metabolic bioprocesses in ccRCC. Alterations of representative proteins depicted as log2 FC (T/TA) (n = 232). Boxplots show the median (central line), the 25–75% IQR (box limits), the ±1.5×IQR (whiskers). e, Differentially expressed one-carbon metabolic enzymes between tumor and adjacent tissues (two-sided t test) and their associations with clinical outcomes (two-sided log-rank test). f Hcy concentrations in tumor and adjacent tissues (n = 24). P values are derived from two-sided paired t test. Data are shown as mean ± SD. g Transcription factors showed both increased/decreased protein expressions and activities in ccRCC tumors. h The increased activity of STAT1 and STAT2 in ccRCC and their association with prognosis (two-sided log-rank test). i Regulatory networks of the TFs and their downstream target proteins. j Abundance fold changes (FCs) for selected highly elevated proteins annotated with potential clinical utilities (n = 232). Drug (FDA-approved drug target), CD marker, and enzyme were annotated by HPA. Metabolism (metabolism-related protein) was annotated by Reactome. Boxplots show the median (central line), the 25–75% IQR (box limits), the min–max (whiskers). k “HPA staining proportions” indicate the proportion of ccRCC sections staining positive for the specific marker in the HPA database.