Oncotarget

Research Papers:

Clinical significance of YAP1 activation in head and neck squamous cell carcinoma

Young-Gyu Eun, Dongjin Lee, Young Chan Lee, Bo Hwa Sohn, Eui Hyun Kim, Sun Young Yim, Kee Hwan Kwon and Ju-Seog Lee _

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Oncotarget. 2017; 8:111130-111143. https://doi.org/10.18632/oncotarget.22666

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Abstract

Young-Gyu Eun1,2, Dongjin Lee1,3, Young Chan Lee2, Bo Hwa Sohn1, Eui Hyun Kim1,4, Sun Young Yim1,5, Kee Hwan Kwon3 and Ju-Seog Lee1

1Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

2Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Republic of Korea

3Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Hallym University, Seoul, Republic of Korea

4Department of Neurosurgery, Severance Hospital, Brain Tumor Center, Yonsei University College of Medicine, Seoul, Republic of Korea

5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea

Correspondence to:

Ju-Seog Lee, email: jlee@mdanderson.org

Keywords: YAP1; gene signature; head and neck cancer; prognosis

Received: February 27, 2017    Accepted: July 18, 2017    Published: November 27, 2017

ABSTRACT

By analyzing the genomic data of head and neck squamous cell cancer (HNSCC), we investigated clinical significance of YAP1 activation. Copy number and mRNA expression of YAP1 were analyzed together to assess clinical relevance of YAP1 activation in HNSCC. The clinical significance of YAP1 activation was further validated in four independent test cohorts. We also assessed the correlation of YAP1 activation with genomic alterations such as copy number alteration, somatic mutation, and miRNA expression. The YAP1-activated (YA) subgroup showed worse prognosis for HNSCC as tested and validated in five cohorts. In a multivariate risk analysis, the YAP1 signature was the most significant predictor of overall survival. The YAP1-inactivated (YI) subgroup was associated with HPV-positive status. In multiplatform analysis, YA tumors had gain of EGFR and SNAI2; loss of tumor-suppressor genes such as CSMD1, CDKN2A, NOTCH1, and SMAD4; and high mutation rates of TP53 and CDKN2A. YI tumors were characterized by gain of PIK3CA, SOX2, and TP63; deletion of 11q23.1; and high mutation rates of NFE2L2, PTEN, SYNE1, and NSD1. YA tumors also showed weaker immune activity as reflected in low IFNG composite scores and YAP1 activity is negatively associated with potential response to treatment of pembrolizumab. In conclusion, activation of YAP1 is associated with worse prognosis of patients with HNSCC and potential resistance to immunotherapy.


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