Decreased Levels of Histone H3K9me1 Indicate Poor Prognosis in Patients with Renal Cell Carcinoma

Background/Aim: To determine the role of global histone H3K9 and H4K20 methylation levels as prognostic parameters in patients with renal cell cancer (RCC). Material and Methods: Global histone methylation levels were investigated in 193 RCC (including 142 clear cell (cc), 31 papillary (p), 10 chromophobe (ch) and 10 sarcomatoid (s) RCC), 10 oncocytomas and 30 benign renal specimens. Results: Histone modifications were mostly similar in the different histological subtypes (p>0.05); significant differences were observed for ccRCC vs. pRCC and pRCC vs. sRCC. Comparing the global H3K9 methylation levels of benign renal tissue with RCC H3K9me1 (histone H3 lysine 9 mono-methylation) (p<0.001), H3K9me2 (histone H3 lysine 9 di-methylation) (j)=0.001) and H3K9me3 (historic H3 lysine 9 tri-methylation) (p<0.001) was significantly over-expressed in benign renal tissue. H3K9 and H4K20 methylation levels were positively correlated to pT-stage (p<0.005) and grading (p<0.05). In localized RCC (n=144), H3K9me1 levels showed a significant correlation with progression-free survival in the univariate model (p=0.034). Conclusion: Global historic methylation levels may help to identify RCC patients with poor prognosis.