KDM4A, KDM4B and KDM4C in non-small cell lung cancer.

KDM4A, KDM4B and KDM4D are lysine demethylases which demethylate H3 at lysine K9 and K36 sites, additionally KDM4D also the H1.4 linker histone at K26 lysine. Lysine methylation changes can repress or induce gene expression at specific sites thus influencing cellular functions. We analysed the immunohistochemical expression of KDM4A, KDM4B and KDM4D in a clinical material of 188 patients with lung carcinomas. There were 132 (70%) squamous cell carcinomas, 53 (28%) adenocarcinomas and 3 (2%) large cell carcinomas in the study. Additionally, the trimethylated state of chromatin was detected with an antibody to trimethylated H3K9 residue. Nuclear KDM4A and KDM4D were associated with the presence of lymph node metastases in tumors. Cytoplasmic KDM4A was associated with poor survival of the patients (P = 0.015) and with a shorter recurrence free interval (P = 0.028). KDM4A and KDM4D appear to have a significant role in the metastatic spread of lung carcinomas. The findings are also in line with their proposed involvement in mechanisms associated with cell proliferation, apoptosis and DNA repair.