P2.01-38 Gene Expression Profiling of CNS Metastases in Non-Small Cell Lung Cancer - Matched Analyses with Primary Tumors

Abstract

Dissemination of non-small cell lung cancer (NSCLC) in the central nervous system (CNS) is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis (BM) versus primary tumour may increase aggressiveness and could explain the worse prognosis of brain metastatic NSCLC. We identified patients with surgically removed BM from NSCLC in two cohorts. The first cohort consisted of 725 patients with surgically removed NSCLC and the second of 280 patients who had received whole brain radiotherapy during the course of their disease. Gene expression analysis with nanoString PanCancer IO 360 panel was performed in BM and primary tumour samples. A minimum of 50 ng of total RNA was used as input for each sample. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software. 30 patients with surgically removed BM were identified from both cohorts. For 13 of these patients primary tumour samples were available. We compared gene expressions in BM with primary tumour samples and found a statistically significant downregulation of certain genes, especially genes related to immune response and immune cell activation. Gene expression profiles from BM samples displayed a distinct clustering pattern compared to primary tumour samples. Results from KEGG-term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG-terms associated with the immune system. We identified a unique gene downregulation pattern in BM samples compared to primary tumour. This finding may explain the lower clinical efficacy of systemic therapy, especially immunotherapy, in BM of NSCLC patients.