DNA Methylation Levels at the C3orf37 Loci Correlate With Prostate Cancer Grade.

[OBJECTIVE] In addition to pathological diagnosis, the identification of a diagnostic index to determine indolent and index cancers will be useful for prostate cancer diagnosis. The present study aimed to provide evidence that quantification of DNA methylation levels at specific gene positions can serve as an indicator for the diagnosis of prostate cancer malignancy.

[METHODS] First, we attempted to identify genomic positions where cancer cells could be discriminated from normal cells using prostate-derived cultured cells by quantification of DNA methylation levels with methylation-specific PCR (MSP). Using needle biopsy tissue from patients with prostate cancer bisected by a tissue divider, we quantified DNA methylation levels at four candidate loci identified in cultured cells and analyzed the pathology. Finally, we examined the correlation between DNA methylation levels and gene expression levels in nearby genomic regions using identical tissue from patients with prostate cancer.

[RESULTS] Quantitative analysis using prostate-derived cultured cells and needle biopsy tissue from prostate cancer patients showed that DNA methylation levels at CpG sites near four genes (BCAT1, C3orf37, PCDHA1-8, and RAI1) were significantly higher in cancer than in normal. In particular, DNA methylation levels near the C3orf37 gene were higher in high-grade cancers compared to intermediate-grade cancers, showing a significant correlation with cancer grade. In addition, a correlation tendency between DNA methylation levels and gene expression levels was found at the PCDHA1 locus among the four genetic loci.

[CONCLUSIONS] Quantitative analysis of DNA methylation at CpG sites near the C3orf37 gene appears to be a promising approach to distinguish between index and indolent prostate cancer cells.