PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma

Oncotarget. 2016 Mar 29;7(13):15901-14. doi: 10.18632/oncotarget.7431.

Abstract

Virus-associated malignancies and sarcomatoid cancers correlate with high PD-L1 expression, however, underlying mechanisms remain controversial. We evaluated the correlation between PD-L1 expression and epithelial-mesenchymal transition (EMT) in head and neck squamous cell carcinomas (HNSCC).Tumor tissues from 50 patients with HNSCC were evaluated for PD-L1 by immunohistochemistry, which showed 32 (64.0%) were PD-L1 positive (PD-L1+). Interestingly, PD-L1 expression was significantly associated with EMT (P = 0.010), as assessed by low E-cadherin and high vimentin expression. The overall survival of PD-L1+ patients with EMT features was significantly worse than those without EMT features (P = 0.007). In an independent validation cohort (N = 91), as well as in HNSCC cases of The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia, high PD-L1 expression was also associated with the high probability of an EMT signature, referred from the GEO dataset, GSE4824. Survival analysis confirmed PD-L1+/EMT+ patients had a poorer prognosis than PD-L1+/EMT- patients in the TCGA cohort. PD-L1 positivity can thus be divided into two categories according to the absence or presence of EMT. PD-L1 expression is also independently associated with EMT features in HNSCC.

Keywords: PD-L1; epithelial-mesenchymal transition; head and neck; p16; squamous.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7-H1 Antigen / biosynthesis*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / pathology*
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Squamous Cell Carcinoma of Head and Neck
  • Young Adult

Substances

  • B7-H1 Antigen
  • CD274 protein, human