High Expression of H3K9me3 Is a Strong Predictor of Poor Survival in Patients With Salivary Adenoid Cystic Carcinoma
Tóm tắt
Context.—Histone methylation and acetylation play important roles in the carcinogenesis and progression of cancer.
Objective.—To investigate whether histone modifications influence the prognosis of patients with salivary adenoid cystic carcinoma (ACC).
Design.—The expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 9 acetylation (H3K9Ac) was assessed by immunohistochemistry in 66 specimens of primary ACC. Tests were used to determine the presence of any correlation between H3K9me3 and H3K9Ac levels and clinicopathologic parameters. Log-rank test and Cox proportional hazards regression models were used to analyze the survival data.
Results.—H3K9me3 expression was positively correlated with solid pattern tumors (P = .002) and distant metastasis (P = .001). Solid pattern tumors had lower H3K9Ac expression levels than cribriform-tubular pattern tumors (P = .03). Patients whose tumors showed high H3K9me3 expression and a solid pattern had a significantly poorer overall survival (OS) (P < .001 and P < .001, respectively) and disease-free survival (P < .001 and P = .01, respectively). Low H3K9Ac expression was correlated with poor OS (P = .05). The multivariate analysis indicated that high levels of H3K9me3 expression and solid pattern tumors were independent prognostic factors that significantly influenced OS (P = .004 and P = .04, respectively). H3K9me3 expression was identified as the only independent predictor of disease-free survival (P = .006).
Conclusions.—Our results suggest that high levels of H3K9me3 expression are predictive of rapid cell proliferation and distant metastasis in ACC. Compared with histologic patterns, H3K9me3 might be a better predictive biomarker for the prognosis of patients with salivary ACC.
Từ khóa
Tài liệu tham khảo
Tian, 2010, Salivary gland neoplasms in oral and maxillofacial regions: a 23-year retrospective study of 6982 cases in an eastern Chinese population, Int J Oral Maxillofac Surg, 39, 235, 10.1016/j.ijom.2009.10.016
van der Wal, 2002, Distant metastases of adenoid cystic carcinoma of the salivary glands and the value of diagnostic examinations during follow-up, Head Neck, 24, 779, 10.1002/hed.10126
Papaspyrou, 2011, Chemotherapy and targeted therapy in adenoid cystic carcinoma of the head and neck: a review, Head Neck, 33, 905, 10.1002/hed.21458
Esteller, 2007, Cancer epigenomics: DNA methylomes and histone-modification maps, Nat Rev Genet, 8, 286, 10.1038/nrg2005
Goel, 2012, Epigenetics of colorectal cancer, Gastroenterology, 143, 1442, 10.1053/j.gastro.2012.09.032
Bhalla, 2005, Epigenetic and chromatin modifiers as targeted therapy of hematologic malignancies, J Clin Oncol, 23, 3971, 10.1200/JCO.2005.16.600
Esteller, 2006, The necessity of a human epigenome project, Carcinogenesis, 27, 1121, 10.1093/carcin/bgl033
Jones, 2002, The fundamental role of epigenetic events in cancer, Nat Rev Genet, 3, 415, 10.1038/nrg816
Li, 2005, Promoter methylation of p16INK4a, RASSF1A, and DAPK is frequent in salivary adenoid cystic carcinoma, Cancer, 104, 771, 10.1002/cncr.21215
Zhang, 2007, Promoter methylation as a common mechanism for inactivating E-cadherin in human salivary gland adenoid cystic carcinoma, Cancer, 110, 87, 10.1002/cncr.22758
Lim, 2011, Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation, J Biol Chem, 286, 13193, 10.1074/jbc.M110.210724
Kondo, 2003, Critical role of histone methylation in tumor suppressor gene silencing in colorectal cancer, Mol Cell Biol, 23, 206, 10.1128/MCB.23.1.206-215.2003
Zhang, 2010, Epigenetic inactivation of the tumor suppressor gene RIZ1 in hepatocellular carcinoma involves both DNA methylation and histone modifications, J Hepatol, 53, 889, 10.1016/j.jhep.2010.05.012
Gencheva, 2010, Regulation of CEACAM1 transcription in human breast epithelial cells, BMC Mol Biol, 11, 79, 10.1186/1471-2199-11-79
Shen, 2011, Nuclear protein isoforms: implications for cancer diagnosis and therapy, J Cell Biochem, 112, 756, 10.1002/jcb.23002
Bernstein, 2005, Genomic maps and comparative analysis of histone modifications in human and mouse, Cell, 120, 169, 10.1016/j.cell.2005.01.001
Pokholok, 2005, Genome-wide map of nucleosome acetylation and methylation in yeast, Cell, 122, 517, 10.1016/j.cell.2005.06.026
Park, 2008, The global histone modification pattern correlates with cancer recurrence and overall survival in gastric adenocarcinoma, Ann Surg Oncol, 15, 1968, 10.1245/s10434-008-9927-9
Song, 2012, Global histone modification pattern associated with recurrence and disease-free survival in non-small cell lung cancer patients, Pathol Int, 62, 182, 10.1111/j.1440-1827.2011.02776.x
Barnes L, Eveson JW, Reichart P, Sidransky D, eds. Pathology and Genetics of Head and Neck Tumours. Lyon, France: IARC Press;2005. World Health Organization Classification of Tumours; vol 9.
Greene FL, Page DL, Fleming ID, eds. AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer;2002.
Kurdistani, 2011, Histone modifications in cancer biology and prognosis, Prog Drug Res, 67, 91
Nishimine, 2003, Alterations of p14ARF and p16INK4a genes in salivary gland carcinomas, Oncol Rep, 10, 555
Nandakumar, 2011, (-)-Epigallocatechin-3-gallate reactivates silenced tumor suppressor genes, Cip1/p21 and p16INK4a, by reducing DNA methylation and increasing histones acetylation in human skin cancer cells, Carcinogenesis, 32, 537, 10.1093/carcin/bgq285
Martin, 2010, Changed genome heterochromatinization upon prolonged activation of the Raf/ERK signaling pathway, PLoS ONE, 5, 10.1371/journal.pone.0013322
Mysliwiec, 2012, Jarid2 (Jumonji, AT rich interactive domain 2) regulates NOTCH1 expression via histone modification in the developing heart, J Biol Chem, 287, 1235, 10.1074/jbc.M111.315945
Lakshmikuttyamma, 2010, Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition, Oncogene, 29, 576, 10.1038/onc.2009.361
Metge, 2010, Elevated osteopontin levels in metastatic melanoma correlate with epigenetic silencing of breast cancer metastasis suppressor 1, Oncology, 78, 75, 10.1159/000292363
Mori, 2005, Epigenetic up-regulation of C-C chemokine receptor 7 and C-X-C chemokine receptor 4 expression in melanoma cells, Cancer Res, 65, 1800, 10.1158/0008-5472.CAN-04-3531
Muller-Tidow, 2010, Profiling of histone H3 lysine 9 trimethylation levels predicts transcription factor activity and survival in acute myeloid leukemia, Blood, 116, 3564, 10.1182/blood-2009-09-240978
Zhen, 2010, The expression of H3K9Ac, H3K14Ac, and H4K20TriMe in epithelial ovarian tumors and the clinical significance, Int J Gynecol Cancer, 20, 82, 10.1111/IGC.0b013e3181ae3efa
Pasini, 2010, Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes, Nucleic Acids Res, 38, 4958, 10.1093/nar/gkq244
Papoutsis, 2011, BRCA-1 promoter hypermethylation and silencing induced by the aromatic hydrocarbon receptor-ligand TCDD are prevented by resveratrol in MCF-7 cells, J Nutr Biochem, 23, 1324, 10.1016/j.jnutbio.2011.08.001
Al-Mamgani, 2012, Adenoid cystic carcinoma of parotid gland treated with surgery and radiotherapy: long-term outcomes, QoL assessment and review of the literature, Oral Oncol, 48, 278, 10.1016/j.oraloncology.2011.10.014