Molecular Characteristics of Liver Metastases from Uveal Melanoma

Abstract

The liver is the most common site of systemic metastases from uveal melanoma (UM). Such metastases usually continue to develop despite the application of current treatment modalities. This study was conducted to obtain insight into the molecular pathways that underlie the development of UM metastasis and thus to identify potential novel therapeutic pathways for this disease. Microarray analysis of seven primary UMs and seven liver metastases from UMs was performed by using oligonucleotide microarrays containing 35,035 features. Bioinformatics was applied to identify expression patterns associated with metastases. Results were validated with real-time quantitative RT-PCR (QPCR) and immunohistochemistry (IHC). Metastasis-associated expression was detected for 193 genes at the false discovery rate (FDR) level of 0%. QPCR confirmed microarray results for all 11 genes that were evaluated (r(2) = 0.9, P = 0.0001), and IHC validated microarray data for the two proteins (NFKB2 and CDK4) that were assessed. The gene expression pattern of UM liver metastases demonstrated a resemblance to normal liver tissue. Bioinformatics facilitate identification of transcription factors, among them NFKB, which potentially regulate expression of several metastasis-associated genes. Liver metastases from UMs have a distinct gene expression pattern compared with the primary tumor while sharing similarities with gene expression patterns of normal liver. Several candidate genes for involvement in UM metastasis have been identified -- among them several in the NFKB pathway.