IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36462-8.html
   My bibliography  Save this article

Integrative proteomic characterization of adenocarcinoma of esophagogastric junction

Author

Listed:
  • Shengli Li

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Precision Research Center for Refractory Diseases, Institute for Clinical Research, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine)

  • Li Yuan

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

  • Zhi-Yuan Xu

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

  • Jing-Li Xu

    (Zhejiang Chinese Medical University)

  • Gui-Ping Chen

    (the First Affiliated Hospital of Zhejiang Chinese Medical University)

  • Xiaoqing Guan

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Guang-Zhao Pan

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Can Hu

    (Zhejiang Chinese Medical University)

  • Jinyun Dong

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Yi-An Du

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

  • Li-Tao Yang

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

  • Mao-Wei Ni

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Rui-Bin Jiang

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Xiu Zhu

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Hang Lv

    (Biological Sample Bank, the First Affiliated Hospital of Zhejiang Chinese Medical University)

  • Han-Dong Xu

    (Zhejiang Chinese Medical University)

  • Sheng-Jie Zhang

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences)

  • Jiang-Jiang Qin

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

  • Xiang-Dong Cheng

    (The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institutes of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences
    Zhejiang Provincial Research Center for Upper Gastrointestinal Tract Cancer, Zhejiang Cancer Hospital
    Zhejiang Key Lab of Prevention, Diagnosis and Therapy of Upper Gastrointestinal Cancer, Zhejiang Cancer Hospital)

Abstract

The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences. The S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression and metastasis in vitro and in vivo. Our comparative analyses reveal distinct genomic features in AEG subtypes. We find a specific decrease of fibroblasts in the S-III subtype. Further phosphoproteomic comparisons reveal different kinase-phosphosubstrate regulatory networks among AEG subtypes. Our proteogenomics dataset provides valuable resources for understanding molecular mechanisms and developing precision treatment strategies of AEG.

Suggested Citation

  • Shengli Li & Li Yuan & Zhi-Yuan Xu & Jing-Li Xu & Gui-Ping Chen & Xiaoqing Guan & Guang-Zhao Pan & Can Hu & Jinyun Dong & Yi-An Du & Li-Tao Yang & Mao-Wei Ni & Rui-Bin Jiang & Xiu Zhu & Hang Lv & Han-, 2023. "Integrative proteomic characterization of adenocarcinoma of esophagogastric junction," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36462-8
    DOI: 10.1038/s41467-023-36462-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36462-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-36462-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sai Ge & Xia Xia & Chen Ding & Bei Zhen & Quan Zhou & Jinwen Feng & Jiajia Yuan & Rui Chen & Yumei Li & Zhongqi Ge & Jiafu Ji & Lianhai Zhang & Jiayuan Wang & Zhongwu Li & Yumei Lai & Ying Hu & Yanyan, 2018. "A proteomic landscape of diffuse-type gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    2. Yuan Lin & Yingying Luo & Yanxia Sun & Wenjia Guo & Xuan Zhao & Yiyi Xi & Yuling Ma & Mingming Shao & Wen Tan & Ge Gao & Chen Wu & Dongxin Lin, 2020. "Genomic and transcriptomic alterations associated with drug vulnerabilities and prognosis in adenocarcinoma at the gastroesophageal junction," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    3. Sai Ge & Xia Xia & Chen Ding & Bei Zhen & Quan Zhou & Jinwen Feng & Jiajia Yuan & Rui Chen & Yumei Li & Zhongqi Ge & Jiafu Ji & Lianhai Zhang & Jiayuan Wang & Zhongwu Li & Yumei Lai & Ying Hu & Yanyan, 2018. "Author Correction: A proteomic landscape of diffuse-type gastric cancer," Nature Communications, Nature, vol. 9(1), pages 1-1, December.
    4. Paul A. Stewart & Eric A. Welsh & Robbert J. C. Slebos & Bin Fang & Victoria Izumi & Matthew Chambers & Guolin Zhang & Ling Cen & Fredrik Pettersson & Yonghong Zhang & Zhihua Chen & Chia-Ho Cheng & Ra, 2019. "Proteogenomic landscape of squamous cell lung cancer," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    5. Ludmil B. Alexandrov & Jaegil Kim & Nicholas J. Haradhvala & Mi Ni Huang & Alvin Wei Tian Ng & Yang Wu & Arnoud Boot & Kyle R. Covington & Dmitry A. Gordenin & Erik N. Bergstrom & S. M. Ashiqul Islam , 2020. "The repertoire of mutational signatures in human cancer," Nature, Nature, vol. 578(7793), pages 94-101, February.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Xiuxiao Tang & Pengguihang Zeng & Kezhi Liu & Li Qing & Yifei Sun & Xinyi Liu & Lizi Lu & Chao Wei & Jia Wang & Shaoshuai Jiang & Jun Sun & Wakam Chang & Haopeng Yu & Hebing Chen & Jiaguo Zhou & Cheng, 2024. "The PTM profiling of CTCF reveals the regulation of 3D chromatin structure by O-GlcNAcylation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Lingling Li & Dongxian Jiang & Hui Liu & Chunmei Guo & Rui Zhao & Qiao Zhang & Chen Xu & Zhaoyu Qin & Jinwen Feng & Yang Liu & Haixing Wang & Weijie Chen & Xue Zhang & Bin Li & Lin Bai & Sha Tian & Su, 2023. "Comprehensive proteogenomic characterization of early duodenal cancer reveals the carcinogenesis tracks of different subtypes," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    2. Yan Li & Chen Xu & Bing Wang & Fujiang Xu & Fahan Ma & Yuanyuan Qu & Dongxian Jiang & Kai Li & Jinwen Feng & Sha Tian & Xiaohui Wu & Yunzhi Wang & Yang Liu & Zhaoyu Qin & Yalan Liu & Jing Qin & Qi Son, 2022. "Proteomic characterization of gastric cancer response to chemotherapy and targeted therapy reveals potential therapeutic strategies," Nature Communications, Nature, vol. 13(1), pages 1-26, December.
    3. Lingling Li & Dongxian Jiang & Qiao Zhang & Hui Liu & Fujiang Xu & Chunmei Guo & Zhaoyu Qin & Haixing Wang & Jinwen Feng & Yang Liu & Weijie Chen & Xue Zhang & Lin Bai & Sha Tian & Subei Tan & Chen Xu, 2023. "Integrative proteogenomic characterization of early esophageal cancer," Nature Communications, Nature, vol. 14(1), pages 1-28, December.
    4. Zhenmei Yao & Ning Xu & Guoguo Shang & Haixing Wang & Hui Tao & Yunzhi Wang & Zhaoyu Qin & Subei Tan & Jinwen Feng & Jiajun Zhu & Fahan Ma & Sha Tian & Qiao Zhang & Yuanyuan Qu & Jun Hou & Jianming Gu, 2023. "Proteogenomics of different urothelial bladder cancer stages reveals distinct molecular features for papillary cancer and carcinoma in situ," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    5. Yan Li & Bing Wang & Wentao Yang & Fahan Ma & Jianling Zou & Kai Li & Subei Tan & Jinwen Feng & Yunzhi Wang & Zhaoyu Qin & Zhiyu Chen & Chen Ding, 2024. "Longitudinal plasma proteome profiling reveals the diversity of biomarkers for diagnosis and cetuximab therapy response of colorectal cancer," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Wenhao Shi & Yushen Wang & Chen Xu & Yan Li & Sai Ge & Bin Bai & Kecheng Zhang & Yunzhi Wang & Nairen Zheng & Juan Wang & Shiqi Wang & Gang Ji & Jipeng Li & Yongzhan Nie & Wenquan Liang & Xiaosong Wu , 2023. "Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    7. Yasuhiko Haga & Yoshitaka Sakamoto & Keiko Kajiya & Hitomi Kawai & Miho Oka & Noriko Motoi & Masayuki Shirasawa & Masaya Yotsukura & Shun-Ichi Watanabe & Miyuki Arai & Junko Zenkoh & Kouya Shiraishi &, 2023. "Whole-genome sequencing reveals the molecular implications of the stepwise progression of lung adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    9. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Teresa Maria Rosaria Noviello & Anna Maria Giacomo & Francesca Pia Caruso & Alessia Covre & Roberta Mortarini & Giovanni Scala & Maria Claudia Costa & Sandra Coral & Wolf H. Fridman & Catherine Sautès, 2023. "Guadecitabine plus ipilimumab in unresectable melanoma: five-year follow-up and integrated multi-omic analysis in the phase 1b NIBIT-M4 trial," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    11. Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    12. Rotem Katzir & Noam Rudberg & Keren Yizhak, 2022. "Estimating tumor mutational burden from RNA-sequencing without a matched-normal sample," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    13. Oriol Pich & Iker Reyes-Salazar & Abel Gonzalez-Perez & Nuria Lopez-Bigas, 2022. "Discovering the drivers of clonal hematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    14. Ewart Kuijk & Onno Kranenburg & Edwin Cuppen & Arne Van Hoeck, 2022. "Common anti-cancer therapies induce somatic mutations in stem cells of healthy tissue," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    15. Taichi Igarashi & Marianne Mazevet & Takaaki Yasuhara & Kimiyoshi Yano & Akifumi Mochizuki & Makoto Nishino & Tatsuya Yoshida & Yukihiro Yoshida & Nobuhiko Takamatsu & Akihide Yoshimi & Kouya Shiraish, 2023. "An ATR-PrimPol pathway confers tolerance to oncogenic KRAS-induced and heterochromatin-associated replication stress," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    16. Sophie Pénisson & Amaury Lambert & Cristian Tomasetti, 2022. "Evaluating cancer etiology and risk with a mathematical model of tumor evolution," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    17. Sujath Abbas & Oriol Pich & Ginny Devonshire & Shahriar A. Zamani & Annalise Katz-Summercorn & Sarah Killcoyne & Calvin Cheah & Barbara Nutzinger & Nicola Grehan & Nuria Lopez-Bigas & Rebecca C. Fitzg, 2023. "Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Sriram Vijayraghavan & Thomas Blouin & James McCollum & Latarsha Porcher & François Virard & Jiri Zavadil & Carol Feghali-Bostwick & Natalie Saini, 2024. "Widespread mutagenesis and chromosomal instability shape somatic genomes in systemic sclerosis," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Josefine Radke & Naveed Ishaque & Randi Koll & Zuguang Gu & Elisa Schumann & Lina Sieverling & Sebastian Uhrig & Daniel Hübschmann & Umut H. Toprak & Cristina López & Xavier Pastor Hostench & Simone B, 2022. "The genomic and transcriptional landscape of primary central nervous system lymphoma," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    20. Eline J. M. Bertrums & Jurrian K. Kanter & Lucca L. M. Derks & Mark Verheul & Laurianne Trabut & Markus J. Roosmalen & Henrik Hasle & Evangelia Antoniou & Dirk Reinhardt & Michael N. Dworzak & Nora Mü, 2024. "Selective pressures of platinum compounds shape the evolution of therapy-related myeloid neoplasms," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36462-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.