Gene expression correlation analysis predicts involvement of high- and low-confidence risk genes in different stages of prostate carcinogenesis.

BACKGROUND

Whole genome association studies have identified many loci associated with the risk of prostate cancer (PC). However, very few of the genes associated with these loci have been related to specific processes of prostate carcinogenesis. Therefore I inferred biological functions associated with these risk genes using gene expression correlation analysis.

METHODS

PC risk genes reported in the literature were classified as having high (P<10(-6)), medium (P<10(-4)), or low (P<10(-2)) statistical confidence. Correlation coefficients of the expression levels between the risk genes and other genes in cancerous prostates samples were compared against those in normal prostates using a microarray dataset from Gene Expression Omnibus.

RESULTS

Overall, significant decrease of correlations in PC was observed between the levels of expression of the high-confidence genes and other genes in the microarray dataset, whereas correlation between low-confidence genes and other genes in PC showed smaller decrease. Genes involved in developmental processes were significantly correlated with all risk gene categories. Ectoderm development genes, which may be related to squamous metaplasia, and genes enriched in fetal prostate stem cells (PSCs) showed strong association with the high-confidence genes. The association between the PSC genes and the low-confidence genes was weak, but genes related to neural system genes showed strong association with low-confidence genes.

CONCLUSIONS

The high-confidence risk genes may be associated with an early stage of prostate carcinogenesis, possibly involving PSCs and squamous metaplasia. The low-confidence genes may be involved in a later stage of carcinogenesis.