Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.

Prognostic value of aberrant promoter hypermethylation of tumor-related genes in early-stage head and neck cancer.
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DOI:
10.18632/oncotarget.8317
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发表时间:
2016-05-03
期刊:
影响因子:
--
通讯作者:
Mineta H
Mineta H
中科院分区:
其他
文献类型:
--
作者:
Misawa K;Mochizuki D;Imai A;Endo S;Mima M;Misawa Y;Kanazawa T;Carey TE;Mineta H

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分期和病理分级对头颈部鳞状细胞癌(HNSCC)的复发有帮助,但不能完全预测复发。因此,预测复发风险的分子生物标记物对于改善临床结果是必要的。采用定量甲基化特异性聚合酶链式反应技术,检测133例HNSCC组织中11个肿瘤相关基因(p16、RASSF1A、E-cadherin、H-cadherin、MGMT、DAPK、DCC、COL1A2、Tac1、SST和GALR1)的甲基化状态。在HNSCC中,p16(44%)、RASSF1A(18%)、E-钙粘素(53%)、H-钙粘素(35%)、MGMT(35%)、DAPK(53%)、DCC(42%)、COL1A2(44%)、Tac1(61%)、SST(%)和GALR1(44%)等基因发生甲基化。6~11位基因甲基化患者的无瘤生存率低于0~5位基因甲基化患者(对数等级检验,P=0.001)。在多变量COX比例风险分析中,E-钙粘素、COL1A2、Tac1和GALR1甲基化与生存不良相关,风险比为4.474(95%CI,1.241-16.124)。在对这四个基因的联合分析中,在早期HNSCC中,带有2-4个甲基化基因的患者的存活率显著低于0-1个甲基化基因的患者。重要的是,一些基因的甲基化与早期HNSCC预后不良密切相关,这为这些高甲基化基因是评估预后的有价值的生物标志物提供了强有力的证据。
Staging and pathological grading are useful, but imperfect predictors of recurrence in head and neck squamous cell carcinoma (HNSCC). Accordingly, molecular biomarkers that predict the risk of recurrence are necessary to improve clinical outcomes. The methylation statuses of the promoters of 11 tumor-related genes (p16, RASSF1A, E-cadherin, H-cadherin, MGMT, DAPK, DCC, COL1A2, TAC1, SST, and GALR1) were analyzed in 133 HNSCC cases using quantitative methylation-specific PCR. We detected frequent methylation of p16 (44%), RASSF1A (18%), E-cadherin (53%), H-cadherin (35%), MGMT (35%), DAPK (53%), DCC (42%), COL1A2 (44%), TAC1 (61%), SST (64%), and GALR1 (44%) in HNSCC. Disease-free survival was lower in patients with 6–11 methylated genes than in those with 0–5 methylated genes (log-rank test, P = 0.001). In a multivariate Cox proportional hazards analysis, the methylation of E-cadherin, COL1A2, TAC1, and GALR1 was associated with poor survival, with hazard ratios of 4.474 (95% CI, 1.241–16.124). In a joint analysis of these four genes, patients with 2–4 methylated genes had a significantly lower survival rate than those with 0–1 methylated genes in early-stage HNSCC. Importantly, the methylation of some genes was closely related to poor prognosis in early-stage HNSCC, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation.
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