Histologic classification of
thymomas has significant limitations with respect to both subtype definitions and consistency. In order to better understand the biology of the disease processes, we performed whole genome gene expression analysis.
RNA was extracted from fresh frozen
tumors from 34 patients with
thymomas and followup data was available. Using the Illumina BeadStudio® platform and Human Ref-8 Beadchip, gene expression data was analyzed with Partek Genomics Suite®, and Ingenuity Pathways Analysis (IPA). Unsupervised clustering of gene expression data, representing one of the largest series in literature, resulted in identification of four molecular clusters of
tumors (C1-C4), which correlated with histology (P = 0.002). However, neither histology nor clusters correlated with clinical outcomes. Correlation of gene expression data with clinical data showed that a number of genes were associated with either advanced stage at diagnosis or development of recurrence or
metastases. The top pathways associated with
metastases were
amino acid metabolisms, biosynthesis of
steroids and
glycosphingolipids, cell cycle checkpoint
proteins and Notch signaling. The differential expression of some of the top genes related to both
metastases and stage was confirmed by RT-PCR in all cases of
metastases and matched nonmetastatic cases. A number of potential candidates for
therapeutics were also identified.