1. Molecular data show conserved DNA locations distinguishing lung cancer subtypes and regulation of immune genes
- Author
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Peter J. van der Spek, Harry J.M. Groen, Maureen Los, Anouk van Schetsen, Bram van Es, T. Jeroen N. Hiltermann, Daan P. Hurkmans, Joachim G.J.V. Aerts, Rogier T A van Wijck, Thu Vu, Tjebbe Tauber, Wouter Karman, Menno Tamminga, Sissy Chen, Ed Schuuring, Tom Peters, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Targeted Gynaecologic Oncology (TARGON), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Translational Immunology Groningen (TRIGR), Internal Medicine, Pathology, and Pulmonary Medicine
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Cancer Research ,Lung Neoplasms ,Microenvironment ,Adenocarcinoma of Lung ,Adenocarcinoma ,NSCLC ,Methylation ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,SDG 3 - Good Health and Well-being ,Carcinoma, Non-Small-Cell Lung ,Squamous cell carcinoma ,REVEALS ,medicine ,Humans ,Epigenetics ,Lung cancer ,Gene ,business.industry ,DNA ,DNA Methylation ,medicine.disease ,Phenotype ,Gene Expression Regulation, Neoplastic ,Immune gene ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,DNA methylation ,Cancer research ,BIOPSY ,business - Abstract
Introduction: Non-small-cell lung cancer exhibits a range of transcriptional and epigenetic patterns that not only define distinct phenotypes, but may also govern immune related genes, which have a major impact on survival.Methods: We used open-source RNA expression and DNA methylation data of the Cancer Genome Atlas with matched non-cancerous tissue to evaluate whether these pretreatment molecular patterns also influenced genes related to the immune system and overall survival.Results: The distinction between lung adenocarcinoma and squamous cell carcinoma are determined by 1083 conserved methylation loci and RNA expression of 203 genes which differ for > 80 % of patients between the two subtypes. Using the RNA expression profiles of 6 genes, more than 95 % of patients could be correctly classified as having either adeno or squamous cell lung cancer. Comparing tumor tissue with matched normal tissue, no differences in RNA expression were found for costimulatory and co-inhibitory genes, nor genes involved in cytokine release. However, genes involved in antigen presentation had a lower expression and a wider distribution in tumor tissue.Discussion: Only a small number of genes, influenced by DNA methylation, determine the lung cancer subtype. The antigen presentation of cancer cells is dysfunctional, while other T cell immune functions appear to remain intact.
- Published
- 2020
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