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Proteogenomic Characterization of Endometrial Carcinoma
Open accessAbstract
We undertook a comprehensive proteogenomic characterization of 95 prospectively collected endometrial carcinomas, comprising 83 endometrioid and 12 serous tumors. This analysis revealed possible new consequences of perturbations to the p53 and Wnt/β-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new information about proteomic markers of clinical and genomic tumor subgroups, including relationships to known druggable pathways. An extensive genome-wide acetylation survey yielded insights into regulatory mechanisms linking Wnt signaling and histone acetylation. We also characterized aspects of the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, identify new molecular associations of potential mechanistic significance in the development of endometrial cancers, and suggest novel approaches for identifying potential therapeutic targets.
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“Collectively, CPTAC and ICPC collaborators have comprehensively characterized 13 cancer types at the proteogenomics level, with all datasets publicly accessible109–117.”
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Self-citation
Metadata
- Authors
- Dou, Y., Kawaler, E. A., Cui Zhou, D., Gritsenko, M. A., Huang, C., Blumenberg, L., Karpova, A., Petyuk, V. A., Savage, S. R., Satpathy, S., Liu, W., Wu, Y., Tsai, C.-F., Wen, B., Li, Z., Cao, S., Moon, J., Shi, Z., Cornwell, M., Wyczalkowski, M. A., Chu, R. K., Vasaikar, S., Zhou, H., Gao, Q., Moore, R. J., Li, K., Sethuraman, S., Monroe, M. E., Zhao, R., Heiman, D., Krug, K., Clauser, K., Kothadia, R., Maruvka, Y., Pico, A. R., Oliphant, A. E., Hoskins, E. L., Pugh, S. L., Beecroft, S. J. I., Adams, D. W., Jarman, J. C., Kong, A., Chang, H.-Y., Reva, B., Liao, Y., Rykunov, D., Colaprico, A., Chen, X. S., Czekański, A., Jędryka, M., Matkowski, R., Wiznerowicz, M., Hiltke, T., Boja, E., Kinsinger, C. R., Mesri, M., Robles, A. I., Rodriguez, H., Mutch, D., Fuh, K., Ellis, M. J., DeLair, D., Thiagarajan, M., Mani, D. R., Getz, G., Noble, M., Nesvizhskii, A. I., Wang, P., Anderson, M. L., Levine, D. A., Smith, R. D., Payne, S. H., Ruggles, K. V., Rodland, K. D., Ding, L., Zhang, B., Liu, T., Fenyö, D., Agarwal, A., Anurag, M., Avtonomov, D., Birger, C., Birrer, M. J., Boca, S. M., Bocik, W. E., Borate, U., Borucki, M., Burke, M. C., Cai, S., Calinawan, A., Carr, S. A., Carter, S., Castro, P., Cerda, S., Chaikin, M., Chan, D. W., Chan, D., Charamut, A., Chen, F., Chen, J., Chen, L., Chen, L. S., Chesla, D., Chheda, M. G., Chinnaiyan, A. M., Chowdhury, S., Cieslik, M. P., Clark, D. J., Cottingham, S., Culpepper, H., Day, J., De Young, S., Demir, E., Dhanasekaran, S. M., Dhir, R., Domagalski, M. J., Dottino, P., Druker, B., Duffy, E., Dyer, M., Edwards, N. J., Edwards, R., Elburn, K., Field, J. B., Francis, A., Gabriel, S., Geffen, Y., Geiszler, D., Gillette, M. A., Godwin, A. K., Grady, P., Hannick, L., Hariharan, P., Hilsenbeck, S., Hindenach, B., Hoadley, K. A., Hong, R., Hostetter, G., Hsieh, J. J., Hu, Y., Ittmann, M. M., Jaehnig, E., Jewell, S. D., Ji, J., Jones, C. D., Karabon, R., Ketchum, K. A., Khan, M., Kim, B.-J., Krek, A., Krubit, T., Kumar-Sinha, C., Leprevost, F. D., Lewis, M., Li, Q. K., Li, Y., Liu, H., Lubinski, J., Ma, W., Madan, R., Malc, E., Malovannaya, A., Mareedu, S., Markey, S. P., Marrero-Oliveras, A., Martignetti, J., McDermott, J., McGarvey, P. B., McGee, J., Mieczkowski, P., Modugno, F., Montgomery, R., Newton, C. J., Omenn, G. S., Paulovich, A. G., Perou, A. M., Petralia, F., Piehowski, P., Polonskaya, L., Qi, L., Richey, S., Robinson, K., Roche, N., Rohrer, D. C., Schadt, E. E., Schnaubelt, M., Shi, Y., Skelly, T., Sokoll, L. J., Song, X., Stein, S. E., Suh, J., Tan, D., Tansil, D., Teo, G. C., Thangudu, R. R., Tognon, C., Traer, E., Tyner, J., Um, K. S., Valley, D. R., Vatanian, N., Vats, P., Velvulou, U., Vernon, M., Wang, L.-B., Wang, Y., Webster, A., Westbrook, T., Wheeler, D., Whiteaker, J. R., Wilson, G. D., Zakhartsev, Y., Zelt, R., Zhang, H., Zhang, Y., Zhang, Z., & Zhao, G.
- Affiliations
- Baylor College of Medicine (US)
- NYU Langone Health (US)
- Pacific Northwest National Laboratory (US)
- Washington University in St. Louis (US)
- Broad Institute (US)
- The University of Texas MD Anderson Cancer Center (US)
- Gladstone Institutes (US)
- Brigham Young University (US)
- University of Michigan (US)
- Icahn School of Medicine at Mount Sinai (US)
- University of Miami (US)
- Wroclaw Medical University (PL)
- Poznan University of Medical Sciences (PL)
- National Cancer Institute (US)
- Frederick National Laboratory for Cancer Research (US)
- University of South Florida (US)
- Corresponding author
- Rodland, Karin D.
- Ding, Li
- Zhang, Bing
- Liu, Tao
- Fenyö, David
- ORCID
- Dou, Yongchao
- Kawaler, Emily A.
- Huang, Chen
- Blumenberg, Lili
- Karpova, Alla
- Petyuk, Vladislav A.
- Savage, Sara R.
- Satpathy, Shankha
- Liu, Wenke
- Wu, Yige
- Tsai, Chia-Feng
- Wen, Bo
- Li, Zhi
- Cao, Song
- Moon, Jamie
- Shi, Zhiao
- Cornwell, MacIntosh
- Wyczalkowski, Matthew A.
- Chu, Rosalie K.
- Vasaikar, Suhas
- Zhou, Hua
- Gao, Qingsong
- Moore, Ronald J.
- Li, Kai
- Sethuraman, Sunantha
- Monroe, Matthew E.
- Zhao, Rui
- Heiman, David
- Krug, Karsten
- Clauser, Karl
- Kothadia, Ramani
- Maruvka, Yosef
- Pico, Alexander R.
- Hoskins, Emily L.
- Pugh, Samuel L.
- Kong, Andy
- Chang, Hui-Yin
- Reva, Boris
- Liao, Yuxing
- Rykunov, Dmitry
- Colaprico, Antonio
- Chen, Xi Steven
- Czekański, Andrzej
- Jędryka, Marcin
- Matkowski, Rafał
- Wiznerowicz, Maciej
- Hiltke, Tara
- Boja, Emily
- Kinsinger, Christopher R.
- Mesri, Mehdi
- Robles, Ana I.
- Rodriguez, Henry
- Mutch, David
- Fuh, Katherine
- Ellis, Matthew J.
- DeLair, Deborah
- Thiagarajan, Mathangi
- Mani, D.R.
- Getz, Gad
- Noble, Michael
- Nesvizhskii, Alexey I.
- Wang, Pei
- Anderson, Matthew L.
- Levine, Douglas A.
- Smith, Richard D.
- Payne, Samuel H.
- Ruggles, Kelly V.
- Rodland, Karin D.
- Ding, Li
- Zhang, Bing
- Liu, Tao
- Fenyö, David
- Agarwal, Anupriya
- Anurag, Meenakshi
- Avtonomov, Dmitry
- Birrer, Michael J.
- Boca, Simina M.
- Bocik, William E.
- Borate, Uma
- Burke, Meghan C.
- Cai, Shuang
- Calinawan, Anna
- Carr, Steven A.
- Chan, Daniel W.
- Chan, Doug
- Chen, Feng
- Chen, Lijun
- Chheda, Milan G.
- Chinnaiyan, Arul M.
- Chowdhury, Shrabanti
- Cieslik, Marcin P.
- Clark, David J.
- Demir, Emek
- Dhanasekaran, Saravana Mohan
- Dhir, Rajiv
- Domagalski, Marcin J.
- Druker, Brian
- Duffy, Elizabeth
- Dyer, Maureen
- Edwards, Nathan J.
- Edwards, Robert
- Francis, Alicia
- Gabriel, Stacey
- Geffen, Yifat
- Geiszler, Daniel
- Gillette, Michael A.
- Godwin, Andrew K.
- Hannick, Linda
- Hoadley, Katherine A.
- Hong, Runyu
- Hostetter, Galen
- Hsieh, James J.
- Hu, Yingwei
- Ittmann, Michael M.
- Jaehnig, Eric
- Jewell, Scott D.
- Ji, Jiayi
- Jones, Corbin D.
- Ketchum, Karen A.
- Kim, Beom-Jun
- Krek, Azra
- Leprevost, Felipe D.
- Li, Qing Kay
- Li, Yize
- Liu, Hongwei
- Ma, Weiping
- Madan, Rashna
- Malc, Ewa
- Malovannaya, Anna
- McGarvey, Peter B.
- Mieczkowski, Piotr
- Modugno, Francesmary
- Omenn, Gilbert S.
- Paulovich, Amanda G.
- Petralia, Francesca
- Piehowski, Paul
- Rohrer, Daniel C.
- Schadt, Eric E.
- Schnaubelt, Michael
- Shi, Yan
- Sokoll, Lori J.
- Song, Xiaoyu
- Stein, Stephen E.
- Suh, James
- Teo, Guo Ci
- Thangudu, Ratna R.
- Tognon, Cristina
- Traer, Elie
- Tyner, Jeffrey
- Vats, Pankaj
- Wang, Liang-Bo
- Wang, Ying
- Westbrook, Thomas
- Wheeler, David
- Whiteaker, Jeffrey R.
- Wilson, George D.
- Zhang, Hui
- Zhang, Yuping
- Zhang, Zhen
- Zhao, Grace
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2020-02
- Volume
- 180
- Issue
- 4
- Pages
- 729-748.e26
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7233456
- OpenAlex
- W3006211741
- Cited by
- 485
- References
- 188
- Citations by year
- 2026: 47 · 2025: 67 · 2024: 82 · 2023: 93 · 2022: 80 · 2021: 82 · 2020: 33
- FWCI
- 45.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
- Funders
- School of Medicine, New York University
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Endometrial and Cervical Cancer Treatments
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Oncology › Ovarian cancer diagnosis and treatment
- Keywords
- endometrial cancer, proteogenomics, endometrioid carcinoma, serous carcinoma, p53 pathway, Wnt/β-catenin signaling, circular RNA, epithelial-mesenchymal transition, histone acetylation, tumor immune microenvironment, neoantigens, cancer-testis antigens, immunotherapy, therapeutic target, tumor subtypes
- MeSH terms
- Acetylation, Animals, Antigens, Neoplasm, Carcinoma, Female, Humans, Phosphorylation, Protein Processing, Post-Translational, Signal Transduction, Gene Expression Regulation, Neoplastic, Endometrial Neoplasms, Microsatellite Repeats, Proteome, Feedback, Physiological, MicroRNAs, Genomic Instability, Mice, Epithelial-Mesenchymal Transition, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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