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.

Project Narrative Here we propose to use metatranscriptomic sequencing of current and former smokers to develop effective biomarkers for lung cancer prediction and to explore the role of microbe-microbe and microbe-host interactions in lung cancer development. Our hope is that this effort will pave the way for early diagnostics and interventions to improve our early diagnostics and strategies for lung cancer prevention.