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1. Author Correction: Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma.

Author

Wu Y, Terekhanova NV, Caravan W, Naser Al Deen N, Lal P, Chen S, Mo CK, Cao S, Li Y, Karpova A, Liu R, Zhao Y, Shinkle A, Strunilin I, Weimholt C, Sato K, Yao L, Serasanambati M, Yang X, Wyczalkowski M, Zhu H, Zhou DC, Jayasinghe RG, Mendez D, Wendl MC, Clark D, Newton C, Ruan Y, Reimers MA, Pachynski RK, Kinsinger C, Jewell S, Chan DW, Zhang H, Chaudhuri AA, Chheda MG, Humphreys BD, Mesri M, Rodriguez H, Hsieh JJ, Ding L, and Chen F

Published
2023
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2. Epigenetic and transcriptomic characterization reveals progression markers and essential pathways in clear cell renal cell carcinoma.

Author

Wu Y, Terekhanova NV, Caravan W, Naser Al Deen N, Lal P, Chen S, Mo CK, Cao S, Li Y, Karpova A, Liu R, Zhao Y, Shinkle A, Strunilin I, Weimholt C, Sato K, Yao L, Serasanambati M, Yang X, Wyczalkowski M, Zhu H, Zhou DC, Jayasinghe RG, Mendez D, Wendl MC, Clark D, Newton C, Ruan Y, Reimers MA, Pachynski RK, Kinsinger C, Jewell S, Chan DW, Zhang H, Chaudhuri AA, Chheda MG, Humphreys BD, Mesri M, Rodriguez H, Hsieh JJ, Ding L, and Chen F

Subjects
Humans, Transcriptome, Epigenesis, Genetic, Tumor Suppressor Proteins genetics, Gene Expression Regulation, Neoplastic, Carcinoma, Renal Cell pathology, Kidney Neoplasms pathology
Abstract

Identifying tumor-cell-specific markers and elucidating their epigenetic regulation and spatial heterogeneity provides mechanistic insights into cancer etiology. Here, we perform snRNA-seq and snATAC-seq in 34 and 28 human clear cell renal cell carcinoma (ccRCC) specimens, respectively, with matched bulk proteogenomics data. By identifying 20 tumor-specific markers through a multi-omics tiered approach, we reveal an association between higher ceruloplasmin (CP) expression and reduced survival. CP knockdown, combined with spatial transcriptomics, suggests a role for CP in regulating hyalinized stroma and tumor-stroma interactions in ccRCC. Intratumoral heterogeneity analysis portrays tumor cell-intrinsic inflammation and epithelial-mesenchymal transition (EMT) as two distinguishing features of tumor subpopulations. Finally, BAP1 mutations are associated with widespread reduction of chromatin accessibility, while PBRM1 mutations generally increase accessibility, with the former affecting five times more accessible peaks than the latter. These integrated analyses reveal the cellular architecture of ccRCC, providing insights into key markers and pathways in ccRCC tumorigenesis., (© 2023. The Author(s).)

Published
2023
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