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Updated: Jun 30, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Bone metastasis in non-small-cell lung cancer: genomic characterization and exploration of potential targets
Jiali Gong1,2,3, Shumin Hu1,2, Qianyun Shan1,2
1Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus), Zhejiang Cancer Hospital, Institute of Basic and Cancer Medicine, Gongshu, Hangzhou, P.R. China.
Background:
Bone metastasis (BM) seriously affects the quality of life and reduces the survival time of patients with non-small-cell lung cancer (NSCLC). The genomic characteristics and potential targets of BMs are yet to be fully explored.
Objective:
To explore the genetic characteristics and potential targets of BM in NSCLC.
Design:
In all, 83 patients with NSCLC were retrospectively selected in this study. Genomic characterization of BMs was explored with the analysis of NGS results from primary tumors and BMs in 6 patients, then combined with NGS results of lung tumors in 16 patients with initial recurrence in bone to analyze mutations potentially associated with BMs, and finally, the correlation was further validated in 61 postoperative patients.
Methods:
The next generation sequencing (NGS) was performed to identify genomic differences between pulmonary primary tumors and BM. Fluorescence in situ hybridization and immunohistochemistry were performed in postoperative tumor tissues from patients who had undergone radical surgery to validate the predictive role of molecular targets for BM. The correlation between cyclin-dependent kinase 4 (CDK4) and BM was evaluated by Pearson's chi-square test. The university of alabama at birminghan cancer data analysis portal (UALCAN) was carried out for the detection of CDK4 expression in lung cancer and the relationship between CDK4 and clinicopathological parameters. The relationship between prognosis and CDK4 expression was analyzed by the Kaplan-Meier plotter.
Results:
The rate of gene amplification was increased (24% versus 36%) while gene substitution/indel was decreased (64% versus 52%) in BMs. The BM-specific mutations were analyzed in 16 recurrent patients which revealed the highest incidence of CDK4 amplification (18.8%). According to the Kaplan-Meier plotter database, the NSCLC patients with high CDK4 gene expression showed poor overall survival (OS) and recurrence-free survival (RFS) (p < 0.05). The incidence of CDK4 amplification tended to be higher in recurrent patients compared to the patients without BM (18.8% versus 4.7%, p = 0.118).
Conclusion:
Compared to the primary tumors of NSCLC, the genome of BMs showed an increased proportion of amplification and a decreased proportion of gene substitution/indel. Furthermore, the CDK4 amplification ratio seemed to be elevated in NSCLC patients with BM which may be associated with poor OS and RFS.
Insights
Genomic analysis of bone metastasis (BM) in non-small-cell lung cancer (NSCLC) reveals increased gene amplification and elevated CDK4 amplification, linked to poorer survival outcomes.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Bone metastasis (BM) significantly impacts non-small-cell lung cancer (NSCLC) patient quality of life and survival.
- Genomic landscape and therapeutic targets of NSCLC bone metastasis remain underexplored.
Purpose of the Study:
- To investigate the genomic characteristics of NSCLC bone metastasis.
- To identify potential therapeutic targets for NSCLC bone metastasis.
Main Methods:
- Retrospective analysis of 83 NSCLC patients.
- Next-generation sequencing (NGS) of primary tumors and bone metastasis samples.
- Validation using fluorescence in situ hybridization, immunohistochemistry, and clinical data analysis (UALCAN, Kaplan-Meier plotter).
Main Results:
- Bone metastasis showed increased gene amplification (36% vs. 24%) and decreased gene substitution/indel (52% vs. 64%) compared to primary tumors.
- CDK4 amplification was the most frequent mutation in bone metastasis (18.8%).
- High CDK4 expression correlated with poor overall survival (OS) and recurrence-free survival (RFS) in NSCLC patients (p < 0.05).
Conclusions:
- NSCLC bone metastasis exhibits distinct genomic alterations, notably increased gene amplification.
- Elevated CDK4 amplification in bone metastasis is associated with adverse clinical outcomes.
- CDK4 may represent a potential therapeutic target for NSCLC patients with bone metastasis.
