1. Spatial immunogenomic patterns associated with lymph node metastasis in lung adenocarcinoma
- Author
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Fanjie Meng, Hao Li, Ruoyi Jin, Airong Yang, Hao Luo, Xiao Li, Peiyu Wang, Yaxing Zhao, Olga Chervova, Kaicheng Tang, Sida Cheng, Bin Hu, Yun Li, Jianpeng Sheng, Fan Yang, David Carbone, Kezhong Chen, and Jun Wang
- Subjects
Lung adenocarcinoma lymph node metastasis ,Genomic signatures ,Tumor immune microenvironment ,Spatial immunogenomic patterns ,Diseases of the blood and blood-forming organs ,RC633-647.5 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Lung adenocarcinoma (LUAD) with lymph node (LN) metastasis is linked to poor prognosis, yet the underlying mechanisms remain largely undefined. This study aimed to elucidate the immunogenomic landscape associated with LN metastasis in LUAD. Methods We employed broad-panel next-generation sequencing (NGS) on a cohort of 257 surgically treated LUAD patients to delineate the molecular landscape of primary tumors and identify actionable driver-gene alterations. Additionally, we used multiplex immunohistochemistry (mIHC) on a propensity score-matched cohort, which enabled us to profile the immune microenvironment of primary tumors in detail while preserving cellular metaclusters, interactions, and neighborhood functional units. By integrating data from NGS and mIHC, we successfully identified spatial immunogenomic patterns and developed a predictive model for LN metastasis, which was subsequently validated independently. Results Our analysis revealed distinct immunogenomic alteration patterns associated with LN metastasis stages. Specifically, we observed increased mutation frequencies in genes such as PIK3CG and ATM in LN metastatic primary tumors. Moreover, LN positive primary tumors exhibited a higher presence of macrophage and regulatory T cell metaclusters, along with their enriched neighborhood units (p
- Published
- 2024
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