H3K4me3 and Wdr82 are associated with tumor progression and a favorable prognosis in human colorectal cancer

Abstract

Histone methylation is closely associated with the occurrence of cancer. Histone H3 trimethylation at lysine 4 (H3K4me3) has been reported to modulate the expression of tumor-associated expression and be altered during the progression of several human cancers. WD Repeat Domain 82 (Wdr82), a key epigenetics-associated factor, is a component of the H3K4me3 methyltransferase complex. An aim of the present study was to determine H3K4me3 and Wdr82 expression and their clinical significances in colorectal cancer (CRC). Immunohistochemistry results demonstrated that the expression level of the H3K4me3 and Wdr82 were significantly decreased in CRC tissues compared with paired noncancerous tissues from 123 patients with CRC. Furthermore, the negative expression of H3K4me3 and Wdr82 expression were significantly associated with lymph node (n=33, P=0.0001) and liver metastasis (n=30, P=0.0001). Additionally, multivariate Cox regression analysis indicated that the low expression level of H3K4me3 or Wdr82 was associated with reduced overall survival (OS, P<0.05), and patients with a low H3K4me3 and Wdr82 expression had a significantly poorer outcome compared with patients with a high expression of H3K4me3 and Wdr82 (P=0.0001), suggesting that H3K4me3 and Wdr82 expression were independent factors for OS in patients with CRC. In conclusion, the decreased expressions of H3K4me3 and Wdr82 were associated with a poor prognosis in CRC. The combined expression of H3K4me3 and Wdr82 may serve as a novel prognostic marker for CRC.