Abstract LB-269: Genome-wide expression profiling of highly degraded formalin-fixed paraffin-embedded tissue from non-small cell lung carcinoma

Abstract

Abstract Microarray-based genome-wide gene expression analysis on fresh frozen tissue is widely used in cancer studies. Compared to fresh frozen tissues, formalin-fixed paraffin-embedded (FFPE) tissues are more accessible in the clinical setting for genomic analysis, but its use has been hampered by technical difficulty. In this study, we investigated the potential use of the Whole-Genome DASL HT Assay (Illumina, San Diego, CA) for global expression profiling (covering >47,000 annotated transcripts) in 24 tumor/non-affected FFPE tissues obtained by biopsy from patients with non-small cell lung cancer (NSCLC). We obtained high-quality microarray data on 11 FFPE samples (46%). The FFPE samples had a relatively lower median call rate of 12.2% (range: 10–14.5%), as compared with those from fresh samples; ranging from 10% to 25%. Among genes differentially expressed between squamous carcinomas and adjacent non-affected lung tissue, we found that the RECK gene, encoding a tumor suppressor of reversion-inducing cysteine-rich protein with Kazal motifs, was decreased strongly in tumors (fold change: -2.7; p=0.018). This finding was consistent with previous reports that there was a significantly lower expression of RECK mRNA in NSCLC tissue in samples with promoter hypermethylation. During pathway-based analysis using GeneGo database, we found that differentially expressed genes were significantly enriched in several pathways, such as the RAS regulation pathways, epithelial-to-mesenchymal transition pathway, WNT signaling pathway, and signal transduction pathway of lung neoplasms. When comparing expression between adenocarcinoma and squamous NSCLC, the differentially expressed genes were clustered in keratin filaments pathway for cytoskeleton remodeling, WNT signaling pathway, and disease pathways related to bronchial neoplasms and NSCLC. The WNT/PCP signaling pathway has been implicated in human carcinogenesis. MAP3K7 is one of the key signaling molecules of non-canonical WNT pathway, which demonstrated high level expression in lung carcinoma but was not expressed in non-affected pulmonary tissues. Our study demonstrated that DASL expression profiling technology, genome-wide expression profiles can be successfully generated from FFPE lung tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-269. doi:10.1158/1538-7445.AM2011-LB-269