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Accession PRJCA012513
Title Integrated Proteogenomic Characterization across Major Histological Types of Pituitary Neuroendocrine Tumors
Relevance Medical
Data types Exome
Phenotype or Genotype
Transcriptome or Gene expression
Organisms Homo sapiens
Description Pituitary neuroendocrine tumor (PitNET) is one of the most common intracranial tumors. Due to its extensive tumor heterogeneity and the lack of high-quality tissues for biomarker discovery, the causative molecular mechanisms are far from being fully defined, therefore more studies are needed to improve the current clinicopathological classification system, and advanced treatment including targeted and immunotherapeutic strategies are yet to be explored. Here, we performed the largest integrative genomics, transcriptomics, proteomics, and phosphoproteomics analysis reported to date in a cohort of 200 PitNET patients. Genomics data indicated that GNAS copy number gain can serve as a reliable diagnostic marker for hyperproliferation of the PIT1 lineage. Proteomics-based classification of PitNETs identified 7 clusters, among which, tumors overexpressing epithelial-mesenchymal transition (EMT) markers clustered into a more invasive subgroup. Further analysis identified potential therapeutic targets, including CDK6, TWIST1, EGFR, and VEGFR2, for different clusters. Immune subtyping to explore the potential for application of immunotherapy in PitNET identified an association between alterations in the JAK1-STAT1-PDL1 axis and immune exhaustion and between changes in the JAK3-STAT6-FOS/JUN axis and immune infiltration. These identified candidate targets were further confirmed in an independent cohort of 750 PitNET patients. This proteogenomic analysis across traditional histological boundaries improves our current understanding of PitNET pathophysiology and suggests novel therapeutic targets and strategies.
Sample scope Multiisolate
Release date 2022-12-09
Grants
Agency program Grant ID Grant title
the National Program on Key Basic Research Project 2019YFA0801900
the National Program on Key Basic Research Project 2019YFC1316000
China Pituitary Adenoma Specialist Council (CPASC) to-Yao-Zhao
National Key R&D Program of China 2017YFA0505102
National Key R&D Program of China 2016YFA0502500
National Key R&D Program of China 2018YFE0201603
National Key R&D Program of China 2017YFA0505101
National Key R&D Program of China 2020YFE0201600
the National High Technology Research and Development Program of China 863 program 2014AA020611
National Natural Science Foundation of China 31770886
National Natural Science Foundation of China 31972933
the Chang Jiang Scholars Program to-Yao-Zhao
Shanghai Municipal Science and Technology Major Project 2017SHZDZX01
the National Program for Support of Top-Notch Young Professionals to-Yao-Zhao
the National Science Fund for Distinguished Young Scholars 81725011
Major Project of Special Development Funds of Zhangjiang National Independent innovation Demonstration Zone ZJ2019-ZD-004
National Natural Science Funds of China U21A20389
CAMS Innovation Fund for Medical Sciences 2021-I2M-C&T-A-025
Clinical Research Plan of SHDC 2020CR2004A
National Natural Science Funds of China 81802495
Shanghai Sailing program 18YF1403400
Shanghai Chenguang Scholar 19CG08
Fudan original research personalized support project to-Chen-Ding
2018 Postdoctoral Innovation Talents Support Program to-Yunzhi-Wang
Submitter Yao Zhao (zhaoyaohs@vip.sina.com)
Organization Huashan Hospital of Fudan University
Submission date 2022-10-15

Project Data

Resource name Description
BioSample (400)  show -