title: Epigenetic Role of Histone 3 Lysine Methyltransferase and Demethylase in Regulating Apoptosis Predicting the Recurrence of Atypical Meningioma.
abstract: Alteration of apoptosis is related with progression and recurrence of atypical meningiomas (AMs). However, no comprehensive study has been conducted regarding histone modification regulating apoptosis in AMs. This study aimed to determine the prognostic values of certain apoptosis-associated factors, and examine the role of histone modification on apoptosis in AMs. The medical records of 67 patients with AMs, as diagnosed during recent 13 yr, were reviewed retrospectively. Immunohistochemical staining was performed on archived paraffin-embedded tissues for pro-apoptotic factors (CASP3, IGFBP, TRAIL-R1, BAX, and XAF1), anti-apoptotic factors (survivin, ERK, RAF1, MDM2, and BCL2), and the histone modifying enzymes (MLL2, RIZ, EZH1, NSD2, KDM5c, JMJD2a, UTX, and JMJD5). Twenty-six (38.8%) patients recurred during the follow-up period (mean duration 47.7 months). In terms of time-to-recurrence (TTR), overexpression of CASP3, TRAIL-R1, and BAX had a longer TTR than low expression, and overexpression of survivin, MDM2, and BCL2 had a shorter TTR than low expression (P<0.05). Additionally, overexpression of MLL2, UTX, and JMJ5 had shorter TTRs than low expression, and overexpression of KDM5c had a longer TTR than low expression. However, in the multi-variate analysis of predicting factors for recurrence, low expression of CASP3 (P<0.001), and BAX (P<0.001), and overexpression of survivin (P=0.007), and MDM2 (P=0.037) were associated with recurrence independently, but any enzymes modifying histone were not associated with recurrence. Conclusively, this study suggests certain apoptosis-associated factors should be associated with recurrence of AMs, which may be regulated epigenetically by histone modifying enzymes.
authors.affiliation: Department of Neurosurgery and Division of Neurooncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Sang Hyuk
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery and Division of Neurooncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Young Min
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Neurosurgery, Dong-A University Medical Center, Dong-A University College of Medicine, Busan, Korea.
authors.forename: Hyung Dong
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery and Division of Neurooncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.
authors.forename: Young Zoon
authors.initials: YZ
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D042421:Histone Code / Q000235:genetics; D056466:Histone Demethylases / Q000235:genetics*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; D056466:Histone Demethylases; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase
keywords: Apoptosis; Atypical Meningioma; Epigenetics; Histone Modification; Recurrence