Integrated Proteomic and Glycoproteomic Characterization of Human High-Grade Serous Ovarian Carcinoma
Yingwei Hu, Jianbo Pan, Punit Shah, Minghui Ao, Stefani N. Thomas, Yang Liu, Lijun Chen, Michael Schnaubelt, David Clark, Henry Rodriguez, Emily S. Boja, Tara Hiltke, Christopher R. Kinsinger, Karin Rodland, Qing Kay Li, Jiang Qian, Zhen Zhang, Daniel W. Chan, Hui Zhang, Akhilesh Pandey, Amanda G. Paulovich, Andrew N. Hoofnagle, Bing Zhang, D.R. Mani, D.C. Liebler, David F. Ransohoff, David Fenyö, David L. Tabb, Douglas A. Levine, Eric Kuhn, Forest M. White, Gordon A. Whiteley, Heng Zhu, Ie‐Ming Shih, Jasmin Bavarva, Jason McDermott, Jeffrey R. Whiteaker, Karen A. Ketchum, Karl R. Clauser, Kelly V. Ruggles, Kimberly Elburn, Li Ding, Linda I. Hannick, Lisa J. Zimmerman, Mark A. Watson, Mathangi Thiagarajan, Matthew J. Ellis, Mauricio Oberti, Mehdi Mesri, Melinda E. Sanders, Melissa Borucki, Michael A. Gillette, M Snyder, Nathan Edwards, Negin Vatanian, Paul A. Rudnick, Peter B. McGarvey, Philip Mertins, R. Reid Townsend, Ratna R. Thangudu, Richard Smith, Robert Rivers, Robert J.C. Slebos, Samuel Payne, Sherri R. Davies, Shuang Cai, Stephen E. Stein, Steven A. Carr, Steven J. Skates, Subha Madhavan, Tao Liu, Xian Chen, Yingming Zhao, Yue Wang, Zhiao Shi
Abstract
Many gene products exhibit great structural heterogeneity because of an array of modifications. These modifications are not directly encoded in the genomic template but often affect the functionality of proteins. Protein glycosylation plays a vital role in proper protein functions. However, the analysis of glycoproteins has been challenging compared with other protein modifications, such as phosphorylation. Here, we perform an integrated proteomic and glycoproteomic analysis of 83 prospectively collected high-grade serous ovarian carcinoma (HGSC) and 23 non-tumor tissues. Integration of the expression data from global proteomics and glycoproteomics reveals tumor-specific glycosylation, uncovers different glycosylation associated with three tumor clusters, and identifies glycosylation enzymes that were correlated with the altered glycosylation. In addition to providing a valuable resource, these results provide insights into the potential roles of glycosylation in the pathogenesis of HGSC, with the possibility of distinguishing pathological outcomes of ovarian tumors from non-tumors, as well as classifying tumor clusters.