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

• Published in: Molecular oncology 2020-05, Vol.14 (5), p.951-963
• Main Authors: Zerdes, Ioannis, Sifakis, Emmanouil G., Matikas, Alexios, Chrétien, Sebastian, Tobin, Nicholas P., Hartman, Johan, Rassidakis, George Z., Bergh, Jonas, Foukakis, Theodoros
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Apoptosis; Biomarkers; Biomarkers, Tumor - metabolism; Blood Cells - cytology; Blood Cells - metabolism; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; CD3 antigen; CD3 Complex - metabolism; CD4 antigen; CD4 Antigens - metabolism; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; CD8 antigen; CD8 Antigens - metabolism; CD8-Positive T-Lymphocytes - cytology; CD8-Positive T-Lymphocytes - metabolism; Cloning; Cohort Studies; Databases, Genetic; DNA microarrays; Epidermal growth factor; ErbB-2 protein; Estrogen receptors; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; gene signatures; Genomes; Humans; Hybridization; Immunohistochemistry; L1 gene; Ligands; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Metastases; Metastasis; Middle Aged; Patients; PD-L1 protein; PD‐L1; Prognosis; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Proportional Hazards Models; Protein expression; Proteins; Receptor, ErbB-2 - genetics; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; RNA-Seq; Tissue Array Analysis; Tumors; Young Adult
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.12654

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