Molecular data show conserved DNA locations distinguishing lung cancer subtypes and regulation of immune genes

Daan P Hurkmans*, Menno Tamminga, Bram van Es, Tom Peters, Wouter Karman, Rogier T A van Wijck, Peter J van der Spek, Tjebbe Tauber, Maureen Los, Anouk van Schetsen, Thu Vu, T Jeroen N Hiltermann, Ed Schuuring, Joachim G J V Aerts, Sissy Chen, Harry J M Groen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)341-349
Number of pages9
JournalLung Cancer
Volume146
Early online date20-Jun-2020
DOIs
Publication statusPublished - Aug-2020

Keywords

  • Methylation
  • DNA
  • Immune gene
  • Microenvironment
  • Lung cancer
  • NSCLC
  • Adenocarcinoma
  • Squamous cell carcinoma
  • REVEALS
  • BIOPSY

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