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

Zhexuan Li; Changhan Chen; Juncheng Wang; Ming Wei; Guancheng Liu; Yuexiang Qin; Li She; Yong Liu; Donghai Huang; Yongquan Tian; Gangcai Zhu; Xin Zhang

doi:10.7717/peerj.10746

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

PeerJ. 2021 Jan 15:9:e10746. doi: 10.7717/peerj.10746. eCollection 2021.

Authors

Zhexuan Li^{1

2

3}, Changhan Chen^{1

2

3}, Juncheng Wang^{1

2

3}, Ming Wei^{1

2

3}, Guancheng Liu^{1

2

3}, Yuexiang Qin^{1

2

3}, Li She^{1

2

3}, Yong Liu^{1

2

3

4}, Donghai Huang^{1

2

3

4}, Yongquan Tian^{1

2

3}, Gangcai Zhu⁵, Xin Zhang^{1

2

3

4}

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, The Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, Hunan, China.
³ Clinical Research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province, Changsha, Hunan, China.
⁴ National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, China.
⁵ Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Abstract

Background: Metastasis 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.

Methods: PLAU 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.

Results: PLAU 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.

Conclusions: PLAU 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.

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

Grants and funding

This research was supported by the Project of Hunan Health Commission (B2019165), the National Natural Science Foundation of China (Nos. 81974424, 81874133, 81772903, and 81602389), the Natural Science Foundation of Hunan Province (Nos. 2020JJ4827, 2019JJ50944, and 2018JJ2630) and the Huxiang Young Talent Project (No. 2018RS3024). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.