Microbiome-host interactions in oral squamous cell carcinoma: a meta-transcriptomic exploratory study

口腔鳞状细胞癌中微生物组与宿主的相互作用：一项宏转录组学探索性研究

• 批准号: 9809205
• 负责人: Nezar Al-Hebshi
• 金额: $ 19.64万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9809205
• 关键词: Accounting; Address; Alcohol consumption; Algorithms; Animal Model; Archaea; Bacteria; Behavior; Big Data; Bioinformatics; Biopsy; Campylobacter; Candida albicans; Cessation of life; Clinical; Complex; Coupled; Data; Data Analyses; Databases; Development; Diagnostic; Epithelium; Fusobacterium nucleatum; Future; Gene Expression; Genes; Genetic Transcription; Human; Human Genome; Human Papillomavirus; In Vitro; Individual; Inflammatory; Interstitial Collagenase; Knowledge; Lipopolysaccharides; Malignant Neoplasms; Maps; Modality; Nature; Oral; Oropharyngeal Neoplasms; Pathway Analysis; Pathway interactions; Play; Porphyromonas gingivalis; Prevotella; Process; Prognostic Marker; Protozoa; Pseudomonas aeruginosa; RNA; Resolution; Ribosomal RNA; Risk Factors; Role; Sampling; Squamous cell carcinoma; Surface; Survival Rate; Taxonomy; The Cancer Genome Atlas; Tissues; Tobacco use; Tumor Tissue; Variant; Virus; Work; bacteriome; base; cancer therapy; carcinogenicity; cohort; deep sequencing; fungus; host microbiome; improved; inflammatory milieu; insight; interest; malignant mouth neoplasm; metatranscriptome; microbial; microbial community; microbial genome; microbial host; microbiome; microbiome analysis; microbiome components; mouth squamous cell carcinoma; mycobiome; neoplastic; neoplastic cell; next generation sequencing; oral carcinogenesis; oral tissue; outcome forecast; tool; transcriptome; transcriptome sequencing; transcriptomics; tumor; tumor behavior; tumor progression

Project summary Oral cancer (predominantly squamous cell carcinoma; OSCC) is the 14th most prevalent malignancy worldwide accounting for more than 300,000 new cases and 145,000 deaths annually. Despite advances in cancer treatment modalities, OSCC continues to have poor prognosis with 5-year survival rates less than 50%. Although use of tobacco and alcohol consumption constitute the major risk factors, there is emerging evidence for the role of microbiome in OSCC. Exploration of such a role has been facilitated by the advent of next generation sequencing and availability of big data analysis tools. However, studies on the association between the microbiome and OSCC has so far focused on compositional analysis, and has been largely limited to the bacterial component of the microbiome. Furthermore, the results from these studies have not been consistent. Our preliminary work demonstrates presence of complex community of microbes other than bacteria including fungi, archaea, viruses and even protists. In addition, it shows that functional analysis generates results that are more consistent, and more importantly, that are directly relevant to the carcinogenic process. In this study, we propose to use RNA sequencing coupled with comprehensive bioinformatic analysis to study the metatranscriptome of OSCC tissues. Specifically, the study will characterize the transcriptional activity (function) as well as composition of the multi-kingdom microbiome associated with OSCC (aim 1), and correlate it with the gene expression of the host (aim 2). The study will provide a new insight into the role microbiome in OSCC by providing preliminary data on the possible mechanisms by which the tumor's microbial community may influence on its behavior.

项目摘要 口腔癌（主要是鳞状细胞癌; OSCC）是第14位最常见的恶性肿瘤 在世界范围内，每年有超过30万例新病例和14.5万例死亡。尽管取得了进展 在癌症治疗方式中，OSCC的预后仍然很差，5年生存率低于 超过50%。虽然吸烟和饮酒是主要的危险因素， 微生物组在口腔鳞状细胞癌中作用的新证据。对这一作用的探索得到了以下方面的推动： 下一代测序的出现和大数据分析工具的可用性。然而，关于 微生物组和口腔鳞状细胞癌之间的联系迄今为止集中在成分分析上， 主要局限于微生物组的细菌成分。此外，来自 这些研究并不一致。我们的初步工作表明， 除细菌外的微生物群落，包括真菌、古细菌、病毒甚至原生生物。在 此外，它还表明，功能分析产生的结果更加一致， 重要的是，这些都与致癌过程直接相关。在这项研究中，我们建议使用RNA 测序结合综合生物信息学分析研究口腔鳞癌的元转录组 组织中具体而言，该研究将表征转录活性（功能）以及 与OSCC相关的多王国微生物组的组成（目的1），并将其与 宿主的基因表达（目的2）。这项研究将为微生物组在疾病中的作用提供新的见解。 通过提供有关肿瘤微生物作用可能机制的初步数据来研究OSCC 社区可能会影响其行为。