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Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma

Author

Listed:
  • Nayoung Kim

    (Samsung Medical Center
    Sungkyunkwan University School of Medicine
    The Catholic University of Korea)

  • Hong Kwan Kim

    (Sungkyunkwan University School of Medicine)

  • Kyungjong Lee

    (Sungkyunkwan University School of Medicine)

  • Yourae Hong

    (Samsung Medical Center
    Sungkyunkwan University)

  • Jong Ho Cho

    (Sungkyunkwan University School of Medicine)

  • Jung Won Choi

    (Sungkyunkwan University School of Medicine)

  • Jung-Il Lee

    (Sungkyunkwan University School of Medicine)

  • Yeon-Lim Suh

    (Sungkyunkwan University School of Medicine)

  • Bo Mi Ku

    (Sungkyunkwan University School of Medicine)

  • Hye Hyeon Eum

    (Samsung Medical Center
    Sungkyunkwan University School of Medicine
    The Catholic University of Korea)

  • Soyean Choi

    (Samsung Medical Center)

  • Yoon-La Choi

    (Sungkyunkwan University
    Sungkyunkwan University School of Medicine
    Sungkyunkwan University School of Medicine)

  • Je-Gun Joung

    (Samsung Medical Center)

  • Woong-Yang Park

    (Samsung Medical Center
    Sungkyunkwan University School of Medicine
    Sungkyunkwan University)

  • Hyun Ae Jung

    (Sungkyunkwan University School of Medicine)

  • Jong-Mu Sun

    (Sungkyunkwan University School of Medicine)

  • Se-Hoon Lee

    (Sungkyunkwan University School of Medicine)

  • Jin Seok Ahn

    (Sungkyunkwan University School of Medicine)

  • Keunchil Park

    (Sungkyunkwan University School of Medicine)

  • Myung-Ju Ahn

    (Sungkyunkwan University School of Medicine)

  • Hae-Ock Lee

    (Samsung Medical Center
    Sungkyunkwan University School of Medicine
    The Catholic University of Korea
    Sungkyunkwan University)

Abstract

Advanced metastatic cancer poses utmost clinical challenges and may present molecular and cellular features distinct from an early-stage cancer. Herein, we present single-cell transcriptome profiling of metastatic lung adenocarcinoma, the most prevalent histological lung cancer type diagnosed at stage IV in over 40% of all cases. From 208,506 cells populating the normal tissues or early to metastatic stage cancer in 44 patients, we identify a cancer cell subtype deviating from the normal differentiation trajectory and dominating the metastatic stage. In all stages, the stromal and immune cell dynamics reveal ontological and functional changes that create a pro-tumoral and immunosuppressive microenvironment. Normal resident myeloid cell populations are gradually replaced with monocyte-derived macrophages and dendritic cells, along with T-cell exhaustion. This extensive single-cell analysis enhances our understanding of molecular and cellular dynamics in metastatic lung cancer and reveals potential diagnostic and therapeutic targets in cancer-microenvironment interactions.

Suggested Citation

  • Nayoung Kim & Hong Kwan Kim & Kyungjong Lee & Yourae Hong & Jong Ho Cho & Jung Won Choi & Jung-Il Lee & Yeon-Lim Suh & Bo Mi Ku & Hye Hyeon Eum & Soyean Choi & Yoon-La Choi & Je-Gun Joung & Woong-Yang, 2020. "Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16164-1
    DOI: 10.1038/s41467-020-16164-1
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    10. Jae-Won Cho & Seyeon Park & Gamin Kim & Heonjong Han & Hyo Sup Shim & Sunhye Shin & Yong-Soo Bae & Seong Yong Park & Sang-Jun Ha & Insuk Lee & Hye Ryun Kim, 2021. "Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
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    14. Z. L. Liu & X. Y. Meng & R. J. Bao & M. Y. Shen & J. J. Sun & W. D. Chen & F. Liu & Y. He, 2024. "Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    15. Hai C. T. Nguyen & Bukyung Baik & Sora Yoon & Taesung Park & Dougu Nam, 2023. "Benchmarking integration of single-cell differential expression," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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    17. Yin Li & Manling Jiang & Ling Aye & Li Luo & Yong Zhang & Fengkai Xu & Yongqi Wei & Dan Peng & Xiang He & Jie Gu & Xiaofang Yu & Guoping Li & Di Ge & Chunlai Lu, 2024. "UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    18. Ido Nofech-Mozes & David Soave & Philip Awadalla & Sagi Abelson, 2023. "Pan-cancer classification of single cells in the tumour microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    19. Roberta Piras & Emily Y. Ko & Connor Barrett & Marco Simone & Xianzhi Lin & Marina T. Broz & Fernando H. G. Tessaro & Mireia Castillo-Martin & Carlos Cordon-Cardo & Helen S. Goodridge & Dolores Vizio , 2022. "circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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