Oncotarget

Research Papers:

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

Chan-Young Ock, Sehui Kim, Bhumsuk Keam _, Miso Kim, Tae Min Kim, Jin-Ho Kim, Yoon Kyung Jeon, Ju-Seog Lee, Seong Keun Kwon, Hun J. Hah, Tack-Kyun Kwon, Dong-Wan Kim, Hong-Gyun Wu, Myung-Whun Sung and Dae Seog Heo

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Oncotarget. 2016; 7:15901-15914. https://doi.org/10.18632/oncotarget.7431

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Abstract

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

Correspondence to:

Bhumsuk Keam, e-mail: [email protected]

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

Received: September 23, 2015     Accepted: February 06, 2016     Published: February 17, 2016

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.


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