title: H4K12 and H3K18 Acetylation Associates With Poor Prognosis in Pancreatic Cancer.
abstract: Epigenetic deregulation may be involved in tumor cell biology, including differentiation, tumor progression, and cell death, and histone acetylation is a major regulatory mechanism of gene transcription. Patterns of global histone modifications have been recently suggested as outcome predictors in cancer patients, but few studies have been conducted on pancreatic ductal adenocarcinomas (PDACs). This study was designed to investigate the predictive value of histone acetylation modifications on PDAC.
  
  
  
  A retrospective clinicopathologic analysis was undertaken in 119 patients diagnosed with PDAC between 2005 and 2011, and immunohistochemistry performed with polyclonal antibodies against H4K12ac, H3K9ac, and H3K18ac. Positive nuclear staining for each histone was measured as the intensity and expression, being classified into low-staining or high-staining groups. Results were analyzed in relation to patients' clinicopathologic parameters.
  
  
  
  There was a positive relationship between tumor differentiation and H4K12ac high scores (P<0.05) and staining with the 3 markers correlated positively with tumor stage (P<0.01). Univariate analysis showed worse survival in patients with high detection levels of H4K12ac (P=0.038) and H3K18Ac (P=0.033). A backwards Cox proportional hazards model analysis revealed the independent prognostic effect of high H4K12ac and H3K18ac levels (hazard ratios of 1.6 and 1.7, respectively, P<0.05), especially for patients at early stages of disease.
  
  
  
  We propose that acetylation of H4K12 and H3K18 may be considered valuable prognostic factors for pancreatic cancer, although the mechanism involved needs further investigation. Increasing insights into histone acetylation modifications can ultimately generate new ideas for rational and molecularly based diagnostic and therapeutic approaches.
authors.affiliation: *Programa de Pós-Graduação em Medicina, Ciências Médicas §Programa de Pós-Graduação em Genética e Biologia Molecular ¶Faculdade de Medicina ††Departamento de Genética §§Programa de Pós-Graduação em Cirurgia, Universidade Federal do Rio Grande do Sul †Serviço de Patologia ∥Laboratório de Medicina Genômica #Instituto do Câncer Infantil e Laboratório de Pesquisas em Câncer **Serviço de Genética Médica ‡‡Serviço de Cirurgia do Aparelho Digestivo, Grupo de Vias Biliares e Pâncreas, Hospital de Clínicas de Porto Alegre, Porto Alegre-RS ‡Centro Integrado de Patologia. Rio Grande-RS, Brazil.
authors.forename: Camila N
authors.initials: CN
authors.lastname: Juliano
authors.forename: Patricia
authors.initials: P
authors.lastname: Izetti
authors.forename: Marcia P
authors.initials: MP
authors.lastname: Pereira
authors.forename: Alex P
authors.initials: AP
authors.lastname: Dos Santos
authors.forename: Charles P
authors.initials: CP
authors.lastname: Bravosi
authors.forename: Ana L
authors.initials: AL
authors.lastname: Abujamra
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Prolla
authors.forename: Alessandro B
authors.initials: AB
authors.lastname: Osvaldt
authors.forename: Maria I A
authors.initials: MI
authors.lastname: Edelweiss
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: D006657:Histones