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The expression of sphingosine kinase-1 in head and neck carcinoma
María M Facchinetti1, Norberto A Gandini, María E Fermento
1Instituto de Investigaciones Bioquímicas Bahía Blanca, INIBIBB-CONICET, Argentina.
Abstract:
Sphingosine kinase-1 (SPHK1) modulates the proliferation, apoptosis and differentiation of keratinocytes through the regulation of ceramide and sphingosine-1-phosphate levels. However, studies on the expression of SPHK1 in human head and neck squamous cell carcinoma (HNSCC) specimens are lacking. Therefore, the aim of the present work was to evaluate SPHK1 expression in human primary HNSCCs and to correlate the results with clinical and anatomopathological parameters. We investigated the expression of this protein by immunohistochemistry performed in tissue microarrays of HNSCC and in an independent cohort of 37 paraffin-embedded specimens. SPHK1 expression was further validated by real-time PCR performed on laser capture-microdissected tissue samples. The positive rate of SPHK1 protein in the cancerous tissues was significantly higher (74%) than that in the nontumor oral tissues (23%), and malignant tissues showed stronger immunoreactivity for SPHK1 than normal matching samples. These results were confirmed by real-time PCR quantification of SPHK1 mRNA. Interestingly, the positive expression of SPHK1 was associated with shorter patient survival time (Kaplan-Meier survival curves) and with the loss of p21 expression. Taken together, these results demonstrate that SPHK1 is upregulated in HNSCC and provide clues of the role SPHK1 might play in tumor progression.
Insights
Sphingosine kinase-1 (SPHK1) is upregulated in head and neck squamous cell carcinoma (HNSCC). Increased SPHK1 expression correlates with poorer patient survival and may play a role in HNSCC progression.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sphingosine kinase-1 (SPHK1) regulates key cellular processes like proliferation and apoptosis.
- SPHK1 influences ceramide and sphingosine-1-phosphate metabolism.
- Limited data exists on SPHK1 expression in human head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To investigate SPHK1 protein and mRNA expression in primary HNSCC specimens.
- To correlate SPHK1 expression with clinical and anatomopathological parameters in HNSCC patients.
Main Methods:
- Immunohistochemistry on HNSCC tissue microarrays and paraffin-embedded specimens.
- Real-time PCR on laser capture-microdissected tissues for SPHK1 mRNA quantification.
- Kaplan-Meier survival analysis to assess the correlation with patient survival.
Main Results:
- SPHK1 protein expression was significantly higher in HNSCC tissues (74%) compared to non-tumor tissues (23%).
- Malignant tissues exhibited stronger SPHK1 immunoreactivity than normal samples, confirmed by real-time PCR.
- Positive SPHK1 expression was associated with shorter patient survival and loss of p21 expression.
Conclusions:
- SPHK1 is demonstrably upregulated in HNSCC.
- SPHK1 upregulation suggests a potential role in HNSCC tumor progression.
- Further research into SPHK1's function in HNSCC is warranted.
