P2.03-05 Biologic Profiling of Brain Metastasis from Non-Small Cell Lung Cancer

Abstract

Bain metastasis develops in approximately 50% of patients with non-small cell lung cancer (NSCLC), resulting in poor prognosis and low health-related quality of life. Immunological microenvironment and functions of ion channels have been indicated to play pertinent roles in epithelial-to-mesenchymal transition (EMT) and its reverse mesenchymal-to-epithelial transition (MET), crucial steps in distant metastasis, but their actual roles in brain metastasis of NSCLC remains unclear. The aim of this study is to investigate biologic profiles of brain metastasis of NSCLC. Formalin-fixed paraffin-embedded (FFPE) samples of brain metastasis and paired primary sites were collected from 3 patients with NSCLC undergoing surgical resection between Jan. 2012 and Dec. 2017. Total RNA was extracted from the archived FFPE, of which integrity was briefly checked by Nanodrop. Gene expression was detected by nCounter (NanoString Technologies, WA, USA) with PanCancer Immune Profilling Panel and custom-made KMU IonChannel Panel that covered selected 100 genes. Detected data was analyzed by nCounter Advanced Analysis (version 2.0.115). Factors with unadjusted P-value < 0.01 were regarded as candidates for further investigation. Brain metastasis showed upregulations of MCOLN3 and YTHDF2 (unadjusted P-value= 0.0093 and 0.0063, respectively) compared to the primary site. Conversely, primary site showed upregulations of IFNAR1, TNFRSF4, CXCL11, CT45A1, MAP3K5, TAL1, LAG3 and MARCO. In LATE-BREAKING ABSTRACT, we will report following data: 1) Immunohistochemistry results of the candidate proteins in resected brain metastasis and primary sites of NSCLC from larger population. In situ hybridization is also planned. 2) Additional data of expression profiles of the candidate genes in sphere cell line from brain metastasis and primary site of NSCLC. Biologic profilings of brain metastasis from NSCLC may subsequently help to understand underlying mechanism and ultimately lead to novel targeted therapy. Further details will be added in LATE-BREAKING ABSTRACT.