In silico functional profiling of individual prostate cancer tumors: many genes, few functions

Identification of genes that are differently expressed is a common approach used to analyze genetic mechanisms underlying cancer development. However, recent study results suggest that many such genes relate to a small number of biological functions. We hypothesized that analysis of these functions provides a better understanding of tumor biology than does actual identification of these genes.

We re-analyzed publicly available gene expression data for paired samples of prostate tumor and adjacent normal tissue from the same patients to identify genes differently expressed in individual tumors and then used them to identify the functions.

We found significant interindividual variation in the type and the number of functions. After adjusting for redundancy and nonspecificity of the functional terms, we identified seven functions. Several of them showed a strong association with clinical traits, e.g. age at diagnosis, preoperative prostate-specific antigen concentration, Gleason grade, and biochemical recurrence. Actin cytoskeleton was the function most frequently associated with clinical traits. Of note, the association between function and clinical traits was much stronger than that between the genes differently expressed and those traits.

Different prostate tumors differ in their functional profiles. Functions of differently expressed genes are strongly associated with clinical traits. This suggests that analysis of functions of differently expressed genes may provide a better description of tumor biology than does analysis of the respective genes.