Microbiome-based biomarkers and models of lung cancer development and treatment

项目总结/摘要 微生物组已成为癌症研究的重要焦点，包括其在预防，诊断， 和机械因果关系。然而，我们对这些机制的理解仍有很大差距， 分子相互作用（微生物-微生物和微生物-宿主）继续阻碍我们的发展能力 有效的基于微生物组的生物标志物用于癌症结果或用于使用微生物组作为癌症靶点 治疗或预防。对于肺癌，最近在研究以下机制作用方面取得了一些进展： 微生物组在肺癌发生中的作用，尽管肺癌微生物组的研究已经落后于进展 在其他癌症。 在这里，我们建议结合使用来自当前和以前吸烟者鼻腔样本的RNA测序数据， 利用最先进的计算模型来开发有效的生物标志物，并探索微生物的作用， 微生物和微生物-宿主相互作用在肺癌中的作用我们将首先开发和验证预测性生物标志物 使用微生物组和宿主基因表达来治疗肺癌。在此过程中，我们还将描述 与癌症状态相关的微生物-微生物相互作用，并评估微生物组与人类的相互作用 致癌和炎症途径。我们还将开发预测模型，用于评估宿主的影响。 和微生物靶向治疗，以及单个微生物或合成微生物移植的影响， 社区.

Project Summary/Abstract The microbiome has become an important focus of cancer research, including its role in prevention, diagnostics, and mechanistic causation. However, there are still significant gaps in our understanding of the mechanisms and molecular interactions (both microbe-microbe and microbe-host) that continue to hinder our abilities to develop effective microbiome-based biomarkers for cancer outcomes or for using the microbiome as a target for cancer treatment or prevention. For lung cancer there has been some recent progress studying the mechanistic role of the microbiome in lung tumorigenesis, although lung cancer microbiome research has lagged behind progress in other cancers. Here we propose to use RNA-sequencing data from nasal samples of current and former smokers in combination with state-of-the art computational modeling to develop effective biomarkers and explore the role of microbe- microbe and microbe-host interactions in lung cancer. We will first develop and validate predictive biomarkers for lung cancer using the microbiome and host gene expression. In the process, we will also characterize microbe-microbe interactions associated with cancer status, and evaluate microbiome interactions with human oncogenic and inflammatory pathways. We will also develop predictive models for assessing the impact of host and microbial targeted therapies, as well as the impact of the transplantation of individual microbes or synthetic communities.