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A Novel Tumor Suppressor SPINK5 Serves as an Independent Prognostic Predictor for Patients with Head and Neck Squamous Cell Carcinoma.

Authors
  • Lv, Zhongjing1, 2
  • Wu, Kun1, 3
  • Qin, Xing1, 3
  • Yuan, Jian2
  • Yan, Ming1, 3
  • Zhang, Jianjun1, 3
  • Wang, Lizhen1, 4
  • Ji, Tong1, 3
  • Cao, Wei1, 3
  • Chen, Wantao1, 3
  • 1 Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. , (China)
  • 2 Department of Stomatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou City, Jiangsu Province, People's Republic of China. , (China)
  • 3 Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, People's Republic of China. , (China)
  • 4 Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China. , (China)
Type
Published Article
Journal
Cancer Management and Research
Publisher
Dove Medical Press Ltd.
Publication Date
Jan 01, 2020
Volume
12
Pages
4855–4869
Identifiers
DOI: 10.2147/CMAR.S236266
PMID: 32606974
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

In our previous study, serine protease inhibitor Kazal-type 5 (SPINK5), which encodes the product of serine protease inhibitor lymphoepithelial Kazal-type-related inhibitor (LEKTI) was found to be down-regulated in head and neck squamous cell carcinoma (HNSCC) using oligonucleotide microarrays. However, the function and clinical implications of SPINK5/LEKTI remain obscure in HNSCC. The endogenous expression level of SPINK5/LEKTI was further verified in 9 HNSCC cell lines and HNSCCs by means of reverse transcription-polymerase chain reaction, real-time PCR, Western blotting and immunohistochemistry. The biological function of SPINK5/LEKTI was investigated in vitro and in vivo experiments. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to determine the correlation between SPINK5/LEKTI expression and clinical outcome. Down-regulation expression of SPINK5/LEKTI was found in six out of nine HNSCC cell lines and in 85.7% HNSCC specimens (P<0.0001). Upon silencing of SPINK5/LEKTI, the cell proliferation, plate colony formation and cell invasion of WU-HN6 cells were significantly increased, while exogenous overexpression of SPINK5/LEKTI, the proliferation, plate colony and invasion of WU-HN13 and HN30 cells were remarkably inhibited with the arrest of G1 cell cycle (P=0.0001, P=0.003, respectively). HNSCC patients with lower LEKTI levels had significantly inferior overall survival compared to those patients with higher LEKTI (P=0.0017) by Kaplan-Meier survival analysis. Univariate and multivariate Cox proportional hazards regression model analysis revealed that LEKTI expression was an independent prognostic predictor for HNSCC patients (HR=0.114, 95% CI:0.044-0.292, P<0.001). Our results demonstrate that SPINK5/LEKTI might be a tumor suppressor in HNSCCs and serve as an independent prognostic predictor for HNSCC patients. © 2020 Lv et al.

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