Early Multi-Omic Cancer Assessment: eMOCA

Introduction

Lung cancer is a leading cause of cancer-related mortality, claiming an estimated 1.8 million lives in 2020. In the EU, lung cancer accounts for 12% of all new cancer diagnoses and 20% of all cancer deaths.

Screening Challenges

Although helpful in identifying early-stage lung cancer, screening programs frequently lead to false positives and overdiagnosis. This is exacerbated by a lack of clinically useful biomarkers to accurately differentiate between lung cancer and indeterminate nodules found in the lung.

Research on Lung Adenocarcinoma

Recent studies on lung adenocarcinoma (LUAD) suggest that microbial and host genomic signatures could be leveraged to develop useful biomarkers in early-stage disease. However, these studies are based on systemic signatures identified using metagenomics in plasma rather than at the site of the disease, the lung.

Focus on Lung Squamous Cell Cancer

Very little research has been done on lung squamous cell cancer (LUSC). It is likely that both microbial and host signatures in the lungs of patients with LUSC, a more centrally located cancer, will be more specific and have stronger predictive power as biomarkers.

Sampling Challenges

Sampling of the lung is difficult and involves invasive procedures such as bronchoscopy.

Novel Methodology

Exhaled breath condensate (EBC) is a novel non-invasive method of collecting lower airway samples, which I will use to evaluate the lung microenvironment in LUSC.

Advanced Techniques

Furthermore, microbial RNA sequencing (metatranscriptome) provides broader and more detailed insight into the active function of microbes in different environments, while metabolomics provides further insight into the by-products of microbial metabolism.

Comprehensive Omic Approach

Applying this unbiased omic approach (metagenome, metatranscriptome, metabolome & transcriptome) to multiple sample types (blood, sputum, EBC & bronchoscopy samples) will allow identification of novel microbial biomarkers capable of:

1. Distinguishing between LUSC and non-malignant nodules
2. Predicting LUSC progression
3. Guiding the development of new targeted treatment approaches in LUSC.