Oral Microbiome Research Laboratory, Department of Oral Health Sciences, Maurice H. Kornberg School of Dentistry, Temple University, Philadelphia, Pennsylvania.
Low level Radiation Research Section, Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre, Mumbai, India.
Cancer Res Commun. 2023 May 8;3(5):807-820. doi: 10.1158/2767-9764.CRC-22-0349. eCollection 2023 May.
Studies on the microbiome of oral squamous cell carcinoma (OSCC) have been limited to 16S rRNA gene sequencing. Here, laser microdissection coupled with brute-force, deep metatranscriptome sequencing was employed to simultaneously characterize the microbiome and host transcriptomes and predict their interaction in OSCC. The analysis involved 20 HPV16/18-negative OSCC tumor/adjacent normal tissue pairs (TT and ANT) along with deep tongue scrapings from 20 matched healthy controls (HC). Standard bioinformatic tools coupled with in-house algorithms were used to map, analyze, and integrate microbial and host data. Host transcriptome analysis identified enrichment of known cancer-related gene sets, not only in TT versus ANT and HC, but also in the ANT versus HC contrast, consistent with field cancerization. Microbial analysis identified a low abundance yet transcriptionally active, unique multi-kingdom microbiome in OSCC tissues predominated by bacteria and bacteriophages. HC showed a different taxonomic profile yet shared major microbial enzyme classes and pathways with TT/ANT, consistent with functional redundancy. Key taxa enriched in TT/ANT compared with HC were , , Human Herpes Virus 6B, and bacteriophage Yuavirus. Functionally, hyaluronate lyase was overexpressed by in TT/ANT. Microbiome-host data integration revealed that OSCC-enriched taxa were associated with upregulation of proliferation-related pathways. In a preliminary validation experiment, infection of SCC25 oral cancer cells with resulted in upregulation of MYC expression. The study provides a new insight into potential mechanisms by which the microbiome can contribute to oral carcinogenesis, which can be validated in future experimental studies.
Studies have shown that a distinct microbiome is associated with OSCC, but how the microbiome functions within the tumor interacts with the host cells remains unclear. By simultaneously characterizing the microbial and host transcriptomes in OSCC and control tissues, the study provides novel insights into microbiome-host interactions in OSCC which can be validated in future mechanistic studies.
口腔鳞状细胞癌（OSCC）的微生物组研究仅限于 16S rRNA 基因测序。在这里，采用激光微切割与强力、深度宏转录组测序相结合的方法，同时对微生物组和宿主转录组进行特征描述，并预测它们在 OSCC 中的相互作用。该分析涉及 20 对 HPV16/18 阴性 OSCC 肿瘤/相邻正常组织（TT 和 ANT）以及 20 名匹配的健康对照者（HC）的深层舌刮片。标准生物信息学工具和内部算法用于映射、分析和整合微生物和宿主数据。宿主转录组分析确定了不仅在 TT 与 ANT 和 HC 之间，而且在 ANT 与 HC 之间存在已知癌症相关基因集的富集，这与局灶性癌变一致。微生物分析确定了 OSCC 组织中一种低丰度但转录活跃的独特多王国微生物组，主要由细菌和噬菌体组成。HC 显示出不同的分类群谱，但与 TT/ANT 共享主要的微生物酶类和途径，这与功能冗余一致。与 HC 相比，TT/ANT 中丰富的关键分类群为 、 、人类疱疹病毒 6B 和噬菌体 Yuavirus。在功能上，TT/ANT 中 过表达透明质酸酶。微生物组-宿主数据的整合表明，OSCC 富集的分类群与增殖相关途径的上调有关。在初步验证实验中，用 感染 SCC25 口腔癌细胞导致 MYC 表达上调。该研究为微生物组如何有助于口腔癌变的潜在机制提供了新的见解，这可以在未来的实验研究中得到验证。
研究表明，一种独特的微生物组与 OSCC 相关，但微生物组在肿瘤内的功能如何与宿主细胞相互作用仍不清楚。通过同时对 OSCC 和对照组织中的微生物组和宿主转录组进行特征描述，该研究为 OSCC 中的微生物组-宿主相互作用提供了新的见解，这可以在未来的机制研究中得到验证。
