PD-L1 expression is associated with epithelial-mesenchymal transition in head and neck squamous cell carcinoma
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Chan-Young Ock1,*, Sehui Kim2,*, Bhumsuk Keam1,3, Miso Kim1, Tae Min Kim1,3, Jin-Ho Kim4, Yoon Kyung Jeon2, Ju-Seog Lee5, Seong Keun Kwon6, J. Hun Hah6, Tack-Kyun Kwon6, Dong-Wan Kim1,3, Hong-Gyun Wu4, Myung-Whun Sung6, Dae Seog Heo1,3
1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
2Department of Pathology, Seoul National University Hospital Seoul, Korea
3Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
4Department of Radiation Oncology, Seoul National University Hospital, Seoul, South Korea
5Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
6Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, South Korea
*These authors have contributed equally to this work
Bhumsuk Keam, e-mail: email@example.com
Keywords: PD-L1, epithelial-mesenchymal transition, head and neck, squamous, p16
Received: September 23, 2015 Accepted: February 06, 2016 Published: February 17, 2016
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.
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