Differences in actionable genomic alterations between brain metastases and non‑brain metastases in patients with non‑small cell lung cancer

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doi:10.3892/ijo.2022.5390

Differences in actionable genomic alterations between brain metastases and non‑brain metastases in patients with non‑small cell lung cancer

Authors:
- Rui Nian
- Huihui Jiang
- Jiangman Zhao
- Wanle Hou
- Hua Zhang
- Jiangtao Ma
- Pengbiao Lv
- Lisha Jiang
- Yongpan Wang
- Yue Xu
- Shouxin Wu
- Jingwei Lou
- Wanjun Li
View Affiliations

Affiliations: Department of Pathology, Affiliated 3201 Hospital of Xi'an Jiaotong University, Shaanxi, Hanzhong 723000, P.R. China, Zhangjiang Center for Translational Medicine, Shanghai Biotecan Pharmaceuticals Co., Ltd., Shanghai 200135, P.R. China, Department of Laboratory Medicine, First Hospital of Laohekou City, Hubei, Xiangyang 441800, P.R. China, Department of Pathology, Hanzhong People's Hospital, Shaanxi, Hanzhong 723000, P.R. China, Medical Laboratory Science, Hanzhong Railway Central Hospital, Shaanxi, Hanzhong 723000, P.R. China, Department of Surgical Oncology, Hanzhong People's Hospital, Shaanxi, Hanzhong 723000, P.R. China
Published online on: July 5, 2022 https://doi.org/10.3892/ijo.2022.5390
Article Number: 100
Copyright: © Nian et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non‑small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture‑based next‑generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non‑BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel‑Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co‑enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non‑BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma‑derived circulating tumor DNA (ctDNA) in the non‑BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non‑BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

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