Identification of genes and pathways associated with cytotoxic T lymphocyte infiltration of serous ovarian cancer

N Leffers, R S N Fehrmann, M J M Gooden, U R J Schulze, K A Ten Hoor, H Hollema, H M Boezen, T Daemen, S. de Jong, H W Nijman, A G J van der Zee

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Abstract

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are predictors of disease-specific survival (DSS) in ovarian cancer. It is largely unknown what factors contribute to lymphocyte recruitment. Our aim was to evaluate genes and pathways contributing to infiltration of cytotoxic T lymphocytes (CTLs) in advanced-stage serous ovarian cancer.

METHODS: For this study global gene expression was compared between low TIL (n=25) and high TIL tumours (n=24). The differences in gene expression were evaluated using parametric T-testing. Selectively enriched biological pathways were identified with gene set enrichment analysis. Prognostic influence was validated in 157 late-stage serous ovarian cancer patients. Using immunohistochemistry, association of selected genes from identified pathways with CTL was validated.

RESULTS: The presence of CTL was associated with 320 genes and 23 pathways (P<0.05). In addition, 54 genes and 8 pathways were also associated with DSS in our validation cohort. Immunohistochemical evaluation showed strong correlations between MHC class I and II membrane expression, parts of the antigen processing and presentation pathway, and CTL recruitment.

CONCLUSION: Gene expression profiling and pathway analyses are valuable tools to obtain more understanding of tumour characteristics influencing lymphocyte recruitment in advanced-stage serous ovarian cancer. Identified genes and pathways need to be further investigated for suitability as therapeutic targets.

Original languageEnglish
Pages (from-to)685-692
Number of pages8
JournalBritish Jounal of Cancer
Volume103
Issue number5
DOIs
Publication statusPublished - 24-Aug-2010

Keywords

  • gene
  • pathway
  • lymphocyte
  • ovarian cancer
  • microarray
  • DOWN-REGULATION
  • SURVIVAL
  • CELLS
  • MICROARRAY
  • EXPRESSION
  • PROGNOSIS
  • THERAPY
  • SAMPLES
  • DESIGN
  • CXCL16

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