Oncotarget. 2016;7(13):15901-14.

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

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제1저자 옥찬영, 김세희 · 교신저자 김범석

PMID 26893364 PMC4941285 DOI 10.18632/oncotarget.7431 IF 5.008 혈액종양내과

소속 (6)

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
Department of Pathology, Seoul National University Hospital Seoul, Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Department of Radiation Oncology, Seoul National University Hospital, Seoul, South Korea.
Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, South Korea.

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-L1epithelial-mesenchymal transitionhead and neckp16squamous

Figures

**Figure 1** PD-L1 expression is associated with epithelial-mesenchymal transition Representative images of immunohistochemical staining with anti-PD-L1 (× 200; A. × 400, B.), anti-E-cadherin (× 200, C.), and anti-vimentin (× 200, D.) are shown. PD-L1 expression was positively correlated with vimentin and negatively correlated with E-cadherin. The number of PD-L1-negative (blue bars) and -positive (red bars) cases according to epithelial-mesenchymal transition (EMT) are shown. The P value from Fisher's exact test is annotated (red). H-scores for E-cadherin (C) and vimentin (D) are plotted according to PD-L1 and p16 statuses. The number of p16- EMT- (green), p16+ EMT- (orange), p16+ EMT+ (pink), and p16- EMT+ (red) cases according to PD-L1 status are shown E.

**Figure 2** Survival analysis according to PD-L1 and epithelial-mesenchymal transition statuses in HNSCC patients of training (A, B) and validation cohorts (C, D) A Kaplan-Meier plot of overall survival (OS; A, C) and progression-free survival (PFS; B, D) according to PD-L1 and epithelial-mesenchymal transition (EMT) statuses. Abbreviations: HNSCC, head and neck squamous cell carcinoma; Ref, reference.

**Figure 3** The epithelial-mesenchymal transition gene expression signature correlates with PD-L1 expression in The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia Significant 75-gene expression signatures, referred from GSE4824 and Bayesian probability to predict EMT changes that favor mesenchymal features in The Cancer Genome Atlas (TCGA) A. and the Cancer Cell Line Encyclopedia (CCLE) cohorts C. as well as PD-L1 expression, are shown as a heatmap. PD-L1 expression was calculated by the log 2 value of its reads per kilobase of transcript per million mapped reads (RPKM) and was compared according to EMT predictions in TCGA B. and CCLE cohorts D.

**Figure 4** Survival analysis according to PD-L1 and epithelial-mesenchymal statuses in The Cancer Genome Atlas cohort A Kaplan-Meier plot of overall survival (OS; A.) and progression-free survival (PFS; B.) according to PD-L1 expression and epithelial-mesenchymal transition (EMT) status. Abbreviation: Ref, reference.

그림 출처: PubMed Central 공개 논문 (PMC4941285)

Conflict of interest statement

CONFLICTS OF INTEREST. All authors have no conflicts of interest to declare.

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