484P - EGFR amplification is the potential driver gene that accelerates brain metastases in NSCLC patients

Background

Metastases in the brain are certainly associated with dismal prognosis. Current therapies have largely failed to prolong the survival of the majority of patients. Experimental animal models have given us a deeper understanding of the complex underlying biology and the translation of these findings will lead to innovative management of patients with brain metastases.

Methods

Patients with brain metastases from non-small cell lung cancer were investigated in Guang Dong Sanjiu Brain Hospital from January 2020 to April 2023. Overall survival (OS) time was considered as the time of diagnosis to the death or last follow-up time. 168-panel sequencing was performed in all the enrolled patients. Radiology documents were also checked and follow-up times were to April 2023. qRT-PCR and western blotting (WB) were used for gene expression analyses in PC9 and H1975 NSCLC cell lines and CCK8 assay, EDU staining, wound healing, and transwell assays were used to assess the in vitro impact of EGFR amplification compared to the control group. Brain metastases mice models were obtained through intracardiac injections in mice and we also analyzed the brain metastases rate. Additionally, we also compared RNA sequencing results in the PC9 cell line that show overexpression of EGFR with the parental cell line.

Results

EGFR amplification was commonly detected in brain metastases patients (41.1%, 21/51) and in this study, we found that patients with EGFR amplification had worsened survival time compared to those patients without such amplification (p＜0.05). EGFR over-expressing cell lines PC9 and H1975 showed significantly enhanced proliferation and infiltration ability compared with parental PC9 and H1975 cell lines in CCK8 assay, EDU staining, wound healing, and transwell assays. Additionally, we found that the brain metastases rate in mice is much higher in EGFR over-expressing PC9 cell lines in contrast to the parental PC9 cell line. Further RNA sequencing from KEGG analysis showed that the different expression genes are mainly concentrated in ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways.

Conclusions

This study identifies EGFR amplification as a potential driver gene that accelerates brain metastases in NSCLC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Guang Dong Sanjiu Brain Hospital.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.