H3K9me3/H4K20me3 Ratio in Circulating Nucleosomes as Potential Biomarker for Colorectal Cancer

Abstract

Detection of cancer-related histone modifications of nucleosomes in the circulating blood may be useful in early cancer diagnosis. We have analyzed the trimethylation of histone H3 lysine 9 (H3K9me3) and histone H4 lysine 9 (H4K20me3), two modifications involved in heterochromatin formation, at pericentric heterochromatin of circulating nucleosomes in the blood plasma of healthy individuals, patients with either colorectal cancer or multiple myeloma. H3K9me3 was found to be decreased in colorectal cancer and increased in multiple myeloma while H4K20me3 levels were similar in all study groups. Therefore, we used the H3K9me3/H4K20me3 ratio for normalizing H3K9me3 concentrations; it significantly distinguished patients with colorectal cancer (median 0.8) from the healthy group (median 3) and multiple myeloma (median 4.7) (both p < 0.001). We conclude that if validated in a larger series of cases the ratio H3K9me3/H4K20me3 might be a potential diagnostic biomarker for colorectal cancer.