Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.
Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.
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DOI：
10.1093/hmg/ddr593
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发表时间：
2012-04-01
影响因子：
3.5
通讯作者：
Eng C
中科院分区：
文献类型：
--
作者：
Bebek G;Bennett KL;Funchain P;Campbell R;Seth R;Scharpf J;Burkey B;Eng C
临床观察和流行病学研究表明，头颈部鳞状细胞癌(HNSCC)的发病率与口腔卫生有关，提示细菌诱导的炎症在其发病机制中起着重要作用。在这里，我们开始探索初步假设，即特定的微生物种群可能通过炎症和HNSCC相关基因的表观遗传修饰而参与HNSCC的发病。通过16S rRNA测序对42例HNSCC患者匹配的肿瘤和邻近正常组织标本进行的微生物组分析表明，与正常组织相比，特定细菌亚群与HNSCC显著相关(P<；0.01)。此外，微生物群可以通过吸烟状况来区分肿瘤(P<；0.008)，但不能通过酒精状况来区分肿瘤(P=0.41)。如果我们关于微生物通过炎症和随后的异常DNA甲基化发生机制联系的假设是正确的，那么我们应该看到相关基因的高甲基化与特定的微生物组相关联。四个以前与HNSCC或炎症相关的基因(MDR1、IL8、RARB、TGFBR2)的甲基化分析表明，与正常口腔粘膜相比，肿瘤样本中的甲基化显著增加。其中，mdr1启动子甲基化与肿瘤中正常黏膜上特定的微生物组特征有关。此外，我们报告mdr1甲基化与两个特定的细菌亚群，肠杆菌科和扁平线虫的区域淋巴结转移相关(P<；各0.001)。这些关联可能导致对HNSCC发病机制的不同的、潜在的更全面的观点，并支持进一步探索机制联系，如果是这样的话，支持新的治疗策略，如去甲基化药物和益生菌辅助剂，特别是对于晚期或难治性疾病的患者。
Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0.01). Furthermore, microbial populations can separate tumors by tobacco status (P < 0.008), but not by alcohol status (P = 0.41). If our subhypothesis regarding a mechanistic link from microorganism to carcinogenesis via inflammation and consequent aberrant DNA methylation is correct, then we should see hypermethylation of relevant genes associate with specific microbiomic profiles. Methylation analysis in four genes (MDR1, IL8, RARB, TGFBR2) previously linked to HNSCC or inflammation shows significantly increased methylation in tumor samples compared with normal oral mucosa. Of these, MDR1 promoter methylation associates with specific microbiomic profiles in tumor over normal mucosa. Additionally, we report that MDR1 methylation correlates with regional nodal metastases in the context of two specific bacterial subpopulations, Enterobacteriaceae and Tenericutes (P < 0.001 for each). These associations may lead to a different, and potentially more comprehensive, perspective on the pathogenesis of HNSCC, and support further exploration of mechanistic linkage and, if so, novel therapeutic strategies such as demethylating agents and probiotic adjuncts, particularly for patients with advanced or refractory disease.
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影响因子：
12.2
作者：
Shen XJ;Rawls JF;Randall T;Burcal L;Mpande CN;Jenkins N;Jovov B;Abdo Z;Sandler RS;Keku TO
通讯作者：
Keku TO
影响因子：
2.3
作者：
Bartsch, Helmut;Nair, Jagadeesan
通讯作者：
Nair, Jagadeesan
影响因子：
3.6
作者：
van der Deen, Margaretha;de Vries, Elisabeth G. E.;Timmer-Bosscha, Hetty
通讯作者：
Timmer-Bosscha, Hetty
DOI：
10.1007/978-1-60327-530-9_5
发表时间：
2009-01-01
期刊：
INFLAMMATION AND CANCER: METHODS AND PROTOCOLS, VOL 2: MOLECULAR ANALYSIS AND PATHWAYS
影响因子：
--
作者：
Suzuki, Hiromu;Toyota, Minoru;Shinomura, Yasuhisa
通讯作者：
Shinomura, Yasuhisa
影响因子：
5.8
作者：
van der Deen M;Timens W;Timmer-Bosscha H;van der Strate BW;Scheper RJ;Postma DS;de Vries EG;Kerstjens HA
通讯作者：
Kerstjens HA