Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer
BackgroundSpread through air spaces (STAS) represents a novel invasion mechanism in adenocarcinoma that considerably influences lung cancer clinical outcomes; however, studies of its mechanisms at the spatial level are lacking.MethodsWe used the NanoString GeoMx digital spatial profiling (DSP) techn...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1567527/full |
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| author | Wenhao Wang Wenhao Zhou Jingli Fan Tao Jiang Guang Yang Congcong Song Siwei Xu Haitao Luo Huining Liu |
| author_facet | Wenhao Wang Wenhao Zhou Jingli Fan Tao Jiang Guang Yang Congcong Song Siwei Xu Haitao Luo Huining Liu |
| author_sort | Wenhao Wang |
| collection | DOAJ |
| description | BackgroundSpread through air spaces (STAS) represents a novel invasion mechanism in adenocarcinoma that considerably influences lung cancer clinical outcomes; however, studies of its mechanisms at the spatial level are lacking.MethodsWe used the NanoString GeoMx digital spatial profiling (DSP) technology to conduct a spatial transcriptomic analysis of surgically resected tissues from non-small-cell lung cancer (NSCLC) patients with or without STAS.ResultsCompared with tumor nests in non-STAS patients, HLA-DRB5 and RASGRF1 were significantly less expressed in compartments of STAS, suggesting their inhibitory roles in the occurrence of STAS. Meanwhile, an increase in CD4 T memory cells and a decrease in B cells were observed in the tumor immune microenvironment of STAS. Furthermore, distinct molecular profiles were observed between tumor cells in tumor nests and in air spaces in STAS patients, which was highlighted by the elevated ITGA2 expression in the air spaces. These results were validated in an independent cohort by multiplex immunofluorescence stainings.ConclusionThis study is the first to use DSP to analyze spatial transcriptomic profiles of NSCLC tumor nests and air space tumors, and it identifies potential module features that may be used for STAS identification and prognosis. |
| format | Article |
| id | doaj-art-8eb77b6bff2d4ed28dcea3f8f09dda5c |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-8eb77b6bff2d4ed28dcea3f8f09dda5c2025-08-20T03:55:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-07-011610.3389/fphar.2025.15675271567527Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancerWenhao Wang0Wenhao Zhou1Jingli Fan2Tao Jiang3Guang Yang4Congcong Song5Siwei Xu6Haitao Luo7Huining Liu8Department of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, ChinaDepartment of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaDepartment of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, ChinaDepartment of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaShenzhen Engineering Center for Translational Medicine of Precision Cancer Immunodiagnosis and Therapy, YuceBio Technology Co., Ltd, Shenzhen, ChinaDepartment of Thoracic Surgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, ChinaBackgroundSpread through air spaces (STAS) represents a novel invasion mechanism in adenocarcinoma that considerably influences lung cancer clinical outcomes; however, studies of its mechanisms at the spatial level are lacking.MethodsWe used the NanoString GeoMx digital spatial profiling (DSP) technology to conduct a spatial transcriptomic analysis of surgically resected tissues from non-small-cell lung cancer (NSCLC) patients with or without STAS.ResultsCompared with tumor nests in non-STAS patients, HLA-DRB5 and RASGRF1 were significantly less expressed in compartments of STAS, suggesting their inhibitory roles in the occurrence of STAS. Meanwhile, an increase in CD4 T memory cells and a decrease in B cells were observed in the tumor immune microenvironment of STAS. Furthermore, distinct molecular profiles were observed between tumor cells in tumor nests and in air spaces in STAS patients, which was highlighted by the elevated ITGA2 expression in the air spaces. These results were validated in an independent cohort by multiplex immunofluorescence stainings.ConclusionThis study is the first to use DSP to analyze spatial transcriptomic profiles of NSCLC tumor nests and air space tumors, and it identifies potential module features that may be used for STAS identification and prognosis.https://www.frontiersin.org/articles/10.3389/fphar.2025.1567527/fullspread through air spacesnon-small-cell lung cancerdigital spatial profilingspatial heterogeneityspatial transcriptome |
| spellingShingle | Wenhao Wang Wenhao Zhou Jingli Fan Tao Jiang Guang Yang Congcong Song Siwei Xu Haitao Luo Huining Liu Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer Frontiers in Pharmacology spread through air spaces non-small-cell lung cancer digital spatial profiling spatial heterogeneity spatial transcriptome |
| title | Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| title_full | Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| title_fullStr | Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| title_full_unstemmed | Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| title_short | Spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| title_sort | spatial deciphering of the transcriptomic heterogeneity of tumor spread through air spaces in lung cancer |
| topic | spread through air spaces non-small-cell lung cancer digital spatial profiling spatial heterogeneity spatial transcriptome |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1567527/full |
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