Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer

Kangjoon Kim; Jibeom Lee; Jeong-Yun Lee; Seung Hyun Yong; Eun Young Kim; Ji Ye Jung; Young Ae Kang; Moo Suk Park; Young Sam Kim; Chang-Myung Oh; Sang Hoon Lee

doi:10.3389/fonc.2023.1148475

Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer

Front Oncol. 2023 Apr 17:13:1148475. doi: 10.3389/fonc.2023.1148475. eCollection 2023.

Authors

Affiliations

¹ Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
² Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.

Abstract

Introduction: Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC).

Methods: A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0).

Results: Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth's bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration.

Conclusions: Given the incidence and favorable outcome of BM in patients with suspected early-stage NSCLC, selective screening with brain MRI may be considered, especially in patients with high-risk features.

Keywords: UNC79; brain metastasis; early stage lung cancer; magnetic resonance imaging; non-small cell lung cancer.

Grants and funding

Severance Hospital Research Fund for Clinical Excellence C-2021-0020 (SL). Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education 2020R1C1C1004999 (C-MO). GIST Research Institute grant funded by the GIST in 2021 (C-MO).