ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Pharmacology of Anti-Cancer Drugs
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1567527
Spatial deciphering the transcriptomic heterogeneity of tumor spread through air space in lung cancer
Provisionally accepted
Wenhao Wang1
Wenhao Zhou2
Jingli Fan1Tao Jiang1Guang Yang1Congcong Song2Siwei Xu1
Haitao Luo2
Huining Liu1*- 1The First hospital of Hebei Medical University, Shijiazhuang, China
- 2YuceBio Technology Co., Ltd., Shenzhen, China
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Background: Spread through air spaces (STAS) represents a novel invasion mechanism in adenocarcinoma and considerably influences lung cancer clinical outcome, but studies of its mechanism at spatial level are lacking.Methods: We used NanoString GeoMx digital spatial profiling (DSP) technology to conduct spatial transcriptomic analysis on surgically resected tissues from non-small cell lung cancer (NSCLC) patients with or without STAS.Results: Compared with tumor nests of non-STAS, the HLA-DRB5 and RASGRF1 significantly lower expressed in compartments of STAS, suggesting their inhibitory roles in the occurrence of STAS. Meanwhile, increase in CD4 T memory cells and 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 air spaces in STAS patients, highlighted by elevated ITGA2 expression in air spaces. These results were validated in an independent cohort by multiple immunofluorescence staining.Conclusions: This study is the first to use DSP for analyzing spatial transcriptomic profiles of NSCLC tumor nests and air space tumors, and identifies potential module features that may be used for STAS identification and prognosis.
Keywords: spread through air spaces, Non-small cell lung cancer, Digital spatial profiling, Spatial heterogeneity, Spatial transcriptome
Received: 27 Jan 2025; Accepted: 23 Jun 2025.
Copyright: © 2025 Wang, Zhou, Fan, Jiang, Yang, Song, Xu, Luo and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huining Liu, The First hospital of Hebei Medical University, Shijiazhuang, China
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