Microarray Analysis Identifies Pathways In Progression of Early Stage Lung Adenocarcinoma: The Importance of Focal Adhesion and ECM-Receptor Interactions

Abstract

Citation Research ABSTRACTRecurrence after lung cancer surgery is high, even among Non-Small Cell Lung Cancer (NSCLC) adenocarcinoma patients diagnosed early as Stage I, where there has been no spread to lymph nodes. Understanding the biological underpinnings of aggressivity and recurrence in this subset of tumours may enable the identification of patients who would benefit from adjuvant therapy. The purpose of this study was to identify differentially expressed molecular biomarkers that might underlie recurrence of Stage I tumours by comparing gene expression in later-stage tumours with those expressed in early-stage tumours. Gene expression in tissue biopsy samples from five Stage I and five Stage II/III NSCLC adenocarcinoma patients was analysed using an oligonucleotide microarray containing 17,000 probes printed in duplicate. Analyses were performed on total RNA isolated from tumour tissue of each patient using universal human RNA as a reference. Compared to normal tissues, the transcriptome of Stage I NSCLC adenocarcinomas showed enrichment in general pathways in cancer, whereas in Stage II/III more specific cancer pathways such as focal adhesion and ECM-receptor interaction pathways were enriched and components of the PPAR signalling pathway were depleted. Relative to early-stage NSCLC, Stage II/III adenocarcinomas showed up-regulation of genes of the basic transcriptional and translational machinery, particularly the "cancer testis antigen" PASD1 transcription factor. The actin cytoskeleton re-organisation and interleukin-6 pathways were also up-regulated whereas there was a generalized down-regulation of immune effectors and genes involved in immune system development. This small-scale transcriptome study provides important information about the pathways and molecules likely to be involved in the more metastatic propensity of those Stage I NSCLC adenocarcinomas that recur.