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

BACKGROUND: 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 micro...

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Detalles Bibliográficos
Autores principales: Lv, Zhongjing, Wu, Kun, Qin, Xing, Yuan, Jian, Yan, Ming, Zhang, Jianjun, Wang, Lizhen, Ji, Tong, Cao, Wei, Chen, Wantao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Original Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320891/
https://www.ncbi.nlm.nih.gov/pubmed/32606974
http://dx.doi.org/10.2147/CMAR.S236266
Descripción
Sumario:BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Our results demonstrate that SPINK5/LEKTI might be a tumor suppressor in HNSCCs and serve as an independent prognostic predictor for HNSCC patients.

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