Interrogating the precancerous evolution of pathway dysfunction in lung squamous cell carcinoma using XTABLE

Author:

Roberts Matthew12,Ogden Julia23,Hossain AS Mukarram12,Chaturvedi Anshuman24,Kerr Alastair RW12ORCID,Dive Caroline12,Beane Jennifer Ellen5,Lopez-Garcia Carlos23ORCID

Affiliation:

1. Cancer Biomarker Centre, Cancer Research UK Manchester Institute, The University of Manchester

2. Cancer Research UK Lung Cancer Centre of Excellence

3. Translational Lung Cancer Biology Laboratory, Cancer Research UK Manchester Institute, University of Manchester

4. Department of Histopathology, The Christie Hospital

5. Boston University School of Medicine

Abstract

Lung squamous cell carcinoma (LUSC) is a type of lung cancer with a dismal prognosis that lacks adequate therapies and actionable targets. This disease is characterized by a sequence of low- and high-grade preinvasive stages with increasing probability of malignant progression. Increasing our knowledge about the biology of these premalignant lesions (PMLs) is necessary to design new methods of early detection and prevention, and to identify the molecular processes that are key for malignant progression. To facilitate this research, we have designed XTABLE (Exploring Transcriptomes of Bronchial Lesions), an open-source application that integrates the most extensive transcriptomic databases of PMLs published so far. With this tool, users can stratify samples using multiple parameters and interrogate PML biology in multiple manners, such as two- and multiple-group comparisons, interrogation of genes of interests, and transcriptional signatures. Using XTABLE, we have carried out a comparative study of the potential role of chromosomal instability scores as biomarkers of PML progression and mapped the onset of the most relevant LUSC pathways to the sequence of LUSC developmental stages. XTABLE will critically facilitate new research for the identification of early detection biomarkers and acquire a better understanding of the LUSC precancerous stages.

Funder

Cancer Research UK

Manchester Biomedical Research Centre

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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