P1.02-074 The Gene Expression Signatures of Pulmonary Adenocarcinoma with Micropapillary Features

Abstract

Invasive lung adenocarcinomas have been classified into 5 subtypes by the new WHO classification, of which the micropapillary-predominant subtype is known to have a poor prognosis. However, we previously reported that lung adenocarcinomas harboring a micropapillary component (MPC) of more than 5% showed poorer disease-free survival and overall survival in comparison to the other subtypes (JTCVS 152: 64-72; 2016), despite the MPC not being predominant. Specific biomarkers for the MPC are yet to be developed for the initial diagnosis of adenocarcinoma with an MPC. Total RNA was extracted from snap frozen archived lung adenocarcinoma samples that had been obtained by radical thoracotomy. The diagnosis of each subtype was made by independent pathologists using formalin-fixed paraffin-embedded samples. Frozen sections were made using the archived frozen sample; RNA was isolated after the confirmation of the diagnosis of each sample. RNA-sequencing was conducted using 22 adenocarcinomas and 3 normal lung tissue samples. The 22 adenocarcinomas included micropapillary (n=6), papillary (n=5), lepidic (n=5), acinar (n=3) and solid (n=3) subtypes. The reads per kilo base of exon per million mapped reads data derived from RNA-sequencing were calculated to analyze the gene expression profiles of the MPCs. The expression levels of the genes were validated by a real-time PCR. A hierarchical clustering analysis revealed a cluster of tumor samples with MPCs. Two hundred four genes were differentially expressed in adenocarcinomas that contain an MPC. A gene-ontology analysis showed the enrichment of signal-related genes, with 50 significantly upregulated genes, including BAMBI, CXCL14 and VSIG1. The results of a gene expression analysis using next generation sequencing revealed the specific gene expression profile of adenocarcinomas that contain an MPC, and several genes might be candidate diagnostic biomarkers for the subtype. In addition, these genes may play an important role in the unique characteristics of adenocarcinomas that contain an MPC.