• Soohwan Choi, Hyung Suk Kim, Kyueng-Whan Min, Yung-Kyun Noh, Jeong-Yeon Lee, Ji-Yong Moon, Un Suk Jung, Mi Jung Kwon, Dong-Hoon Kim, Byoung Kwan Son, Jung Soo Pyo, and Sun Kyun Ro.
• Department of Thoracic and Cardiovascular Surgery, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.
• J. Korean Med. Sci. 2024 Jan 15; 39 (2): e16e16.

BackgroundTumor spread through air spaces (STAS) is a recently discovered risk factor for lung adenocarcinoma (LUAD). The aim of this study was to investigate specific genetic alterations and anticancer immune responses related to STAS. By using a machine learning algorithm and drug screening in lung cancer cell lines, we analyzed the effect of Janus kinase 2 (JAK2) on the survival of patients with LUAD and possible drug candidates.MethodsThis study included 566 patients with LUAD corresponding to clinicopathological and genetic data. For analyses of LUAD, we applied gene set enrichment analysis (GSEA), in silico cytometry, pathway network analysis, in vitro drug screening, and gradient boosting machine (GBM) analysis.ResultsThe patients with STAS had a shorter survival time than those without STAS (P < 0.001). We detected gene set-related downregulation of JAK2 associated with STAS using GSEA. Low JAK2 expression was related to poor prognosis and a low CD8+ T-cell fraction. In GBM, JAK2 showed improved survival prediction performance when it was added to other parameters (T stage, N stage, lymphovascular invasion, pleural invasion, tumor size). In drug screening, mirin, CCT007093, dihydroretenone, and ABT737 suppressed the growth of lung cancer cell lines with low JAK2 expression.ConclusionIn LUAD, low JAK2 expression linked to the presence of STAS might serve as an unfavorable prognostic factor. A relationship between JAK2 and CD8+ T cells suggests that STAS is indirectly related to the anticancer immune response. These results may contribute to the design of future experimental research and drug development programs for LUAD with STAS.© 2023 The Korean Academy of Medical Sciences.

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