Overexpressed PLAU and its potential prognostic value in head and neck squamous cell carcinoma

PeerJ

article

Zhexuan Li¹  Changhan Chen¹  Juncheng Wang¹  Ming Wei¹  Guancheng Liu¹  Yuexiang Qin¹  Li She¹  Yong Liu¹  Donghai Huang¹  Yongquan Tian¹  Gangcai Zhu⁵  Xin Zhang¹ 

[1] Department of Otolaryngology-Head and Neck Surgery, The Xiangya Hospital, Central South University;Otolaryngology Major Disease Research Key Laboratory of Hunan Province;Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province;National Clinical Research Center for Geriatric Disorders;Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University

关键词: The plasminogen activator urokinase (PLAU);    Head and neck squamous cell carcinomas (HNSCC);    The Cancer Genome Atlas (TCGA);    Bioinformatics analysis;    Gene Expression Omnibus (GEO);    Survival;   

DOI  :  10.7717/peerj.10746

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundMetastasis is a major event for survival and prognosis in patients with head and neck squamous cell carcinomas (HNSCC). A primary cause of metastasis is the proteolytic degradation of the extracellular matrix (ECM). The plasminogen activator urokinase (PLAU) is involved in the transformation of plasminogen to plasmin leading to hydrolyzation of ECM-related proteins. However, the role of PLAU expression in HNSCC is unclear and the worth being investigated.MethodsPLAU expression profiles and clinical parameters from multiple HNSCC datasets were used to investigate the relationship of PLAU expression and HNSCC survival. GO and PPI network were established on PLAU-related downstream molecular. The stroma score was deconvoluted for analysis of PLAU’s association with the immune environment. ROC analysis was applied to show the performance of PLAU in predicting HNSCC prognosis.ResultsPLAU mRNA was significantly elevated, as opposed to its methylation, in HNSCC tumor samples over normal specimens (all p < 0.01). Univariate and multivariate cox analysis showed PLAU could be an independent indicator for HNSCC prognosis. Combining with neck lymph node status, the AUC of PLAU in predicting 5-years overall survival reached to 0.862. GO enrichment analysis showed the major biological process (extracellular matrix organization and the P13K-Akt signaling pathway) may involve to the possible mechanism of PLAU’s function on HNSCC prognosis. Furthermore, PLAU expression was positively correlated with stroma cell score, M1 type macrophages, and negatively associated with CD4 + T cell, Tregs cell, and follicular helper T cell.ConclusionsPLAU might be an independent biomarker for predicting outcomes of HNSCC patients. The elevated expression of PLAU was associated with HPV positivity and neck node status. The PI3K-Akt pathway and aberrant proportions of immune cells might underly the mechanism of PLAU’s oncogene role in HNSCC.

【 授权许可】

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