MA24.03 Biologic Profiling of Pre-Metastatic Niche in Completely Resected Pathological Stage I Non-Small Cell Lung Cancer

Abstract

Despite refinement of treatment strategy for non-small cell lung cancer (NSCLC), pathological Stage I NSCLC still develops recurrent disease in approximately 20% of patients even after complete resection. Recently, tumor microenvironment which promotes distant metastasis, or 'pre-metastatic niche', has been indicated to play pertinent roles in postoperative recurrence of cancer. Our aim is to investigate biologic profiles of pre-metastatic niche in pathological Stage I NSCLC. Eighteen (12.7%) of 141 patients with pathological Stage IA or IB NSCLC who underwent R0 lobectomy between Jan. 2008 and Dec. 2013 developed distant metastasis postoperatively. From archived formalin-fixed paraffin-embedded specimens, these 18 cases of postoperative distant metastasis and matched cases were selected for total RNA extraction. To overcome inherent bias in selecting control patients, one-to-one matched pairs were created using propensity score matching of which model included age, sex, smoking history, and pathological stage. The samples with inadequate mRNA quality/ quantity were excluded. Gene expressions were detected by nCounter (NanoString Technologies, WA, USA) with PanCancer Immune Profilling Panel and PanCancer Progression Panel. Detected expressions were then analyzed and compared between the two groups by nCounter Advanced Analysis (version 2.0.115). Genes with unadjusted P-value < 0.01 were regarded as candidates for further investigation From preliminary comparative study on 6 paired cases, distant metastasis group showed upregulations of TPM2, CCL21, SOX2, CXCL12, EGFL7, PTGDS, BGN, PS8L1, ID4 and TGFB, whereas it showed downregulations of MTOR and CCL8 compared to recurrence-free group. In LATE-BREAKING ABSTRACT, we will report following results: 1) Complete dataset of the comparative analysis including all pairs with adequate mRNA. 2) Immunohistochemstry and/or in situ hybridization of the candidate genes/proteins on pathological sections. Biologic profilings of brain metastasis from NSCLC may subsequently help to understand underlying mechanism of postoperative distant metastasis and ultimately lead to novel targeted therapy. Futher details will be added in LATE-BREAKING ABSTRACT.