Molecular Oncology (May 2020)

Programmed death‐ligand 1 gene expression is a prognostic marker in early breast cancer and provides additional prognostic value to 21‐gene and 70‐gene signatures in estrogen receptor‐positive disease

  • Ioannis Zerdes,
  • Emmanouil G. Sifakis,
  • Alexios Matikas,
  • Sebastian Chrétien,
  • Nicholas P. Tobin,
  • Johan Hartman,
  • George Z. Rassidakis,
  • Jonas Bergh,
  • Theodoros Foukakis

DOI
https://doi.org/10.1002/1878-0261.12654
Journal volume & issue
Vol. 14, no. 5
pp. 951 – 963

Abstract

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Gene and protein expression of programmed death‐ligand 1 (PD‐L1) are prognostic in early breast cancer (BC), but their prognostic information is inconsistent at least in some biological subgroups. The validated prognostic gene signatures (GS) in BC are mainly based on proliferation and estrogen receptor (ER)‐related genes. Here, we aimed to explore the prognostic capacity of PD‐L1 expression at the protein vs mRNA levels and to investigate the prognostic information that PD‐L1 can potentially add to routinely used GS. Gene expression data were derived from two early BC cohorts (cohort 1: 562 patients; cohort 2: 1081 patients). Tissue microarrays from cohort 1 were immunohistochemically (IHC) stained for PD‐L1 using the SP263 clone. GS scores (21‐gene, 70‐gene) were calculated, and likelihood‐ratio (LR) tests and concordance indices were used to evaluate the additional prognostic information for each signature. The immune cell composition was also evaluated using the CIBERSORT in silico tool. PD‐L1 gene and protein expressions were independently associated with better prognosis. In ER+/HER2− patients, PD‐L1 gene expression provided significant additional prognostic information beyond that of both 21‐GS [LR‐Δχ2 = 15.289 and LR‐Δχ2 = 8.812, P < 0.01 for distant metastasis‐free interval (DMFI) in cohorts 1 and 2, respectively] and 70‐GS score alone (LR‐Δχ2 = 18.198 and LR‐Δχ2 = 8.467, P < 0.01 for DMFI in cohorts 1 and 2, respectively). PD‐L1 expression was correlated with IHC‐determined CD3+ cells (r = 0.41, P < 0.001) and with CD8+ (r = 0.62, P < 0.001) and CD4+ memory activated (r = 0.66, P < 0.001) but not with memory resting (r = −0.063, P = 0.14) or regulatory (r = −0.12, P < 0.01) T cells in silico. PD‐L1 gene expression represents a promising favorable prognostic marker and can provide additional prognostic value to 21‐ and 70‐gene scores in ER+/HER2− BC.

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