Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas.
Microbiomic differences in tumor and paired-normal tissue in head and neck squamous cell carcinomas.
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DOI：
10.1186/s13073-017-0405-5
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发表时间：
2017-02-07
期刊：
影响因子：
12.3
通讯作者：
Eng C
中科院分区：
文献类型：
--
作者：
Wang H;Funchain P;Bebek G;Altemus J;Zhang H;Niazi F;Peterson C;Lee WT;Burkey BB;Eng C
虽然肠道微生物组在炎症和结直肠癌中的作用最近受到了广泛关注，但很少有数据支持口腔微生物组与头颈部鳞状细胞癌之间的关联。先前的研究仅限于比较从口腔表面拭子获得的微生物群。本研究旨在确定121例头颈部鳞状细胞癌患者配对肿瘤和非肿瘤组织样本中的微生物组学差异，并将这些差异与临床病理特征相关联。从169例患者的配对正常和肿瘤切除标本中提取总DNA;最终分析包括来自121例患者的242个样本。使用16 S rDNA扩增子测序确定每个样品的微生物组含量。使用QIIME算法进行生物信息学分析。在R.中进行聚类强度的F检验、配对肿瘤-正常样本的差异相对丰度的Wilcoxon符号秩检验和T分期与相对丰度的相关性的Wilcoxon秩和检验。我们观察到肿瘤和正常组织之间α多样性的测量没有显著差异（Shannon指数：p = 0.13，系统发育多样性：p = 0.42）。类似地，尽管我们观察到组织类型之间的加权（p = 0.01）和未加权（p = 0.04）Unifrac距离存在统计学显著差异，但肿瘤/正常分组仅解释了样本中总体变化的一小部分（加权R2 = 0.01，未加权R2 < 0.01）。然而，值得注意的是，当比较匹配的肿瘤和正常组织对之间的个体分类群的相对丰度时，我们观察到放线菌及其高达门水平的亲本分类群在肿瘤中相对于正常组织显著耗尽（q < 0.01），而微小单胞菌在肿瘤中相对于正常组织增加（q = 0.01）。这些差异在更广泛的疾病患者中更明显，如通过更高的T分期测量的。配对分析个别肿瘤-正常对显示显着差异的相对丰度的特定类群，即在属放线菌。这些差异在T分期较高的患者中更为明显。我们的观察结果表明，进一步的实验，以询问潜在的新机制相关的致癌与口腔微生物组的改变，可能会对人类宿主的后果。本文的在线版本（doi：10.1186/s13073-017-0405-5）包含补充材料，可供授权用户使用。
While the role of the gut microbiome in inflammation and colorectal cancers has received much recent attention, there are few data to support an association between the oral microbiome and head and neck squamous cell carcinomas. Prior investigations have been limited to comparisons of microbiota obtained from surface swabs of the oral cavity. This study aims to identify microbiomic differences in paired tumor and non-tumor tissue samples in a large group of 121 patients with head and neck squamous cell carcinomas and correlate these differences with clinical-pathologic features. Total DNA was extracted from paired normal and tumor resection specimens from 169 patients; 242 samples from 121 patients were included in the final analysis. Microbiomic content of each sample was determined using 16S rDNA amplicon sequencing. Bioinformatic analysis was performed using QIIME algorithms. F-testing on cluster strength, Wilcoxon signed-rank testing on differential relative abundances of paired tumor-normal samples, and Wilcoxon rank-sum testing on the association of T-stage with relative abundances were conducted in R. We observed no significant difference in measures of alpha diversity between tumor and normal tissue (Shannon index: p = 0.13, phylogenetic diversity: p = 0.42). Similarly, although we observed statistically significantly differences in both weighted (p = 0.01) and unweighted (p = 0.04) Unifrac distances between tissue types, the tumor/normal grouping explained only a small proportion of the overall variation in the samples (weighted R2 = 0.01, unweighted R2 < 0.01). Notably, however, when comparing the relative abundances of individual taxa between matched pairs of tumor and normal tissue, we observed that Actinomyces and its parent taxa up to the phylum level were significantly depleted in tumor relative to normal tissue (q < 0.01), while Parvimonas was increased in tumor relative to normal tissue (q = 0.01). These differences were more pronounced among patients with more extensive disease as measured by higher T-stage. Matched pairs analysis of individual tumor-normal pairs revealed significant differences in relative abundance of specific taxa, namely in the genus Actinomyces. These differences were more pronounced among patients with higher T-stage. Our observations suggest further experiments to interrogate potential novel mechanisms relevant to carcinogenesis associated with alterations of the oral microbiome that may have consequences for the human host. The online version of this article (doi:10.1186/s13073-017-0405-5) contains supplementary material, which is available to authorized users.