Proteogenomic analysis of pediatric and AYA high-grade glioma reveals age-dependent biology, female-male differences, and kinase targets

作者：Nicole L. Tignor, Mateusz Koptyra, Shrabanti Chowdhury, Francesca Petralia, Marina Gritsenko, Weiping Ma, Yuankun Zhu, Giacomo B. Marino, Xiaoyu Song, Simona Migliozzi, Jeffrey R. Whiteaker, Dmitry Rykunov, Yingwei Hu, Noshad Hosseini, Jo Lynne Rokita, Felipe da Veiga Leprevost, Komal S. Rathi, Lijun Chen, Yi-Ting Wang, Karl Weitz, Rosalie Chu, Ronald J. Moore, Azra Krek, Weijia Fu, Xuran Wang, Eden Z. Deng, Chia‐Feng Tsai, Tyler J. Sagendorf, Vladislav Petyuk, Tujin Shi, Thomas Fillmore, Rui Zhao, Matthew E. Monroe, Marius Dannappel, Paul Daniel, Lei Zhao, Richard G. Ivey, Uliana J. Voytovich, Tomer M. Yaron, Emily M. Huntsman, Jared L. Johnson, Nakib Abedin, Yan‐Chak Li, Mariarita Santi, Demetri Dupal, Jena Lilly, Adam Kraya, Joseph M. Dybas, Bo Zhang, Chuwei Zhong, Miguel Brown, Saksham Phul, Eric Wafula, Alvin Farrel, Zhuangzhuang Geng, Ryan J. Corbett, Ammar S. Naqvi, Daniel P. Miller, Jennifer Mason, Tatiana S. Patton, Stephanie B McGrory, Shannon Robins, A. D. HEATH, Catherine Sullivan, Noel Coleman, Allison Morgan, Luciano Garofano, Boris Reva, Eric E. Schadt, Richard D. Smith, Mehdi Mesri, Ana I. Robles, Lewis C. Cantley, Li Ding, KD Rodland, Bing Zhang, Alexey I. Nesvizhskii, Antonio Iavarone, Marcin Cieslik, Joseph E. Ippolito, Phillip B. Storm, Joshua B. Rubin, Ron Firestein, Avi Ma’ayan, Hui Zhang, Amanda G. Paulovich, Tao Liu, Adam C. Resnick, Brian R. Rood, Pei Wang, Jasmin Hussain, Elizabeth Appert, Zev A. Binder, Timothy Prior, Eileen Maloney, Atom Sarkar, Alan R. Turtz, Michael Weaver, Scott Shepard, Kevin Judy, Donald O'Rourke, Nduka Amankulor, Iyad Alnahhas, Pascal Jabbour, Valeria Lopez-gil, Alicia C. Lenzen, Angela Waanders, Javad Nazarian, Jason Fangusaro, Tobey J. MacDonald, Eric H. Raabe, Eric Jackson, Stacie L. Stapleton, Toba Niazi, Shelly Wang, Matija Snuderl, Jessica R. Clymer, Sarah Leary, Nicholas Alexander Vitanza, Michelle Monje, Laura M. Prolo, Sonia Partap, Donald Parsons, Austin J. Stuckert, Michael Fisher, Jane Minturn, Jessica Foster, Peter Madsen, Cassie Kline, Ian F. Pollack, Nalin Gupta, Mike Prados, Joanna J. Phillips, Sabine Mueller, Jeff Greenfield, Nadia Dahmane, Samuel Cheshier, Angela Viaene, Thinh Nguyen, Zeinab Helili, Bailey Farrow, Nathan Young, Nick Van Kuren, Jasmin H. Bavarva, Xu Zhang, Eunkyung An, Kenneth Aldape, Liang-Bo Wang, Song Cao, Bo Wen, Xinpei Yi, Zhiao Shi, Antonio Colaprico, William Bocik, Sandra S. Garcia-Buntley, Ratna Rajesh Thangudu, Alexander R. Pilozzi, Karen A. Ketchum, Shuang Cai, Nathan J. Edwards, Steven A. Carr, Michael A. Gillette, Shankha Satpathy, Daniel W. Chan, DR Mani, Gad A. Getz, Saravana M. Dhanasekaran, Jeffrey W Tyner, Brian Druker, Paul Piehowski, Akhilesh Pandey, RAFAEL RICARDO AURELIANO DA FONSECA, Diwakar Davar, Ramaswamy Govindan, Peter McGarvey, Toan Le, Kristen Nyce, Yin Lu · 发表于：Cell Reports Medicine · 年份：2026 · DOI：10.1016/j.xcrm.2026.103024 · 研究领域：Glioma Diagnosis and Treatment、Protein Degradation and Inhibitors、Advanced Proteomics Techniques and Applications

High-grade gliomas (HGGs) in children and adolescents and young adults (AYA) exhibit distinct biology across the neurodevelopmental spectrum. To dissect tumor-intrinsic molecular characteristics independent of developmental variation, we perform comprehensive proteogenomic analyses of tumors from 112 HGG patients aged 0-40 years. Our multi-omics analysis identifies two AYA subgroups-adolescents (aged 15-26 years) and young adults (aged 26-40 years)-with distinct molecular profiles and survival outcomes. Tumor-normal comparisons and survival modeling highlight roles of oxidative phosphorylation and neuronal system biology in glioma progression. Causal network analysis and cell line studies provide a rationale for personalized therapies targeting candidate kinases, such as CDK8. Survival modeling, clustering, and immune-landscape analyses identify proteins, post-translational modifications, and immune signatures linked to outcomes and reveal clinically relevant differences between male and female patients.