Abstract 110P
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 searched in Guang Dong Sanjiu Brain Hospital from January 2020 to April 2023. Overall survival (OS) time was accelerated from the time of IV diagnosis to the death or last follow-up time. 168-panel sequencing was performed in all the enrolled patients. Radiology documents are also checked and follow-up times were last to the April of 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 metastase mice models were obtained through intracardiac injections in mice and we also analyzed the brain metastase rate. Additionally, we also compare RNA sequencing results in the PC9 cell line that overexpression EGFR with parental cell line.
Results
EGFR amplification was commonly detected in brain metastase 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-expression 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 metastase rate in mice is much higher in EGFR over-expression 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
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.