Spatially resolved gene expression profiling of tumor microenvironment reveals key steps of lung adenocarcinoma development

Yuma Takano, Jun Suzuki, Kotaro Nomura, Gento Fujii, Junko Zenkoh, Hitomi Kawai, Yuta Kuze, Yukie Kashima, Satoi Nagasawa, Yuka Nakamura, Motohiro Kojima, Katsuya Tsuchihara, Masahide Seki, Akinori Kanai, Daisuke Matsubara, Takashi Kohno, Masayuki Noguchi, Akihiro Nakaya, Masahiro Tsuboi, Genichiro Ishii, Yutaka Suzuki () and Ayako Suzuki ()
Additional contact information
Yuma Takano: Graduate School of Frontier Sciences, The University of Tokyo
Jun Suzuki: National Cancer Center Hospital East
Kotaro Nomura: National Cancer Center Hospital East
Gento Fujii: Graduate School of Frontier Sciences, The University of Tokyo
Junko Zenkoh: Graduate School of Frontier Sciences, The University of Tokyo
Hitomi Kawai: University of Tsukuba
Yuta Kuze: Graduate School of Frontier Sciences, The University of Tokyo
Yukie Kashima: Graduate School of Frontier Sciences, The University of Tokyo
Satoi Nagasawa: Graduate School of Frontier Sciences, The University of Tokyo
Yuka Nakamura: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Motohiro Kojima: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Katsuya Tsuchihara: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Masahide Seki: Graduate School of Frontier Sciences, The University of Tokyo
Akinori Kanai: Graduate School of Frontier Sciences, The University of Tokyo
Daisuke Matsubara: University of Tsukuba
Takashi Kohno: National Cancer Center Research Institute
Masayuki Noguchi: University of Tsukuba
Akihiro Nakaya: Graduate School of Frontier Sciences, The University of Tokyo
Masahiro Tsuboi: National Cancer Center Hospital East
Genichiro Ishii: Exploratory Oncology Research and Clinical Trial Center, National Cancer Center
Yutaka Suzuki: Graduate School of Frontier Sciences, The University of Tokyo
Ayako Suzuki: Graduate School of Frontier Sciences, The University of Tokyo

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract The interaction of tumor cells and their microenvironment is thought to be a key factor in tumor development. We present spatial RNA profiles obtained from 30 lung adenocarcinoma patients at the non-invasive and later invasive stages. We use spatial transcriptome sequencing data in conjunction with in situ RNA profiling to conduct higher resolution analyses. The detailed examination of each case, as well as the subsequent computational analyses based on the observed diverse profiles, reveals that significant changes in the phenotypic appearances of tumor cells are frequently associated with changes in immune cell features. The phenomenon coincides with the induction of a series of cellular expression programs that enable tumor cells to transform and break through the immune cell barrier, allowing them to progress further. The study shows how lung tumors develop through interaction in their microenvironments.

Date: 2024
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DOI: 10.1038/s41467-024-54671-7

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