Sphingosine kinase‑1 predicts overall survival outcomes in non‑small cell lung cancer patients treated with carboplatin and navelbine

Gachechiladze,Mariam; Tichý,Tomáš; Kolek,Vítězslav; Grygárková,Ivona; Klein,Jiří; Mgebrishvili,Giorgi; Kharaishvili,Gvantsa; Janíková,Mária; Smičková,Petra; Cierna,Lucia; Pitson,Stuart; Maddelein,Marie‑Lise; Cuvillier,Olivier; Škarda,Jozef

doi:10.3892/ol.2019.10447

Sphingosine kinase‑1 predicts overall survival outcomes in non‑small cell lung cancer patients treated with carboplatin and navelbine

Authors:
- Mariam Gachechiladze
- Tomáš Tichý
- Vítězslav Kolek
- Ivona Grygárková
- Jiří Klein
- Giorgi Mgebrishvili
- Gvantsa Kharaishvili
- Mária Janíková
- Petra Smičková
- Lucia Cierna
- Stuart Pitson
- Marie‑Lise Maddelein
- Olivier Cuvillier
- Jozef Škarda
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Affiliations: Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, 77515 Olomouc, Czech Republic, Department of Tuberculosis and Respiratory Diseases, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital in Olomouc, 77900 Olomouc, Czech Republic, 1st Department of Surgery, Faculty of Medicine and Dentistry, Palacký University and Faculty Hospital in Olomouc, 77900 Olomouc, Czech Republic, Faculty of Medicine and Dentistry, Palacký University Olomouc, 77515 Olomouc, Czech Republic, Centre for Cancer Biology, University of South Australia and SA Pathology, Adelaide SA5000, Australia, Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France
Published online on: June 7, 2019 https://doi.org/10.3892/ol.2019.10447
Pages: 1259-1266
Copyright: © Gachechiladze et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Sphingosine 1‑phosphate (S1P) is a bioactive lipid metabolite associated with cancer cell proliferation, survival, migration and regulation of tumor angiogenesis in various cellular and animal models. Sphingosine kinase‑1 (SphK1) and S1P lyase are the main enzymes that respectively control the synthesis and degradation of S1P. The present study analyzed the prognostic and predictive value of SphK1 and S1P lyase expression in patients with non‑small cell lung cancer (NSCLC), treated with either surgery alone or in combination with adjuvant carboplatin and navelbine. Formalin‑fixed, paraffin‑embedded tissue samples from 176 patients with NSCLC were stained immunohistochemically using antibodies against SphK1 and S1P lyase, and their expression was correlated with all available clinicopathological factors. Increased expression of SphK1 was significantly associated with shorter overall and disease free survival in patients treated with adjuvant platinum‑based chemotherapy. No prognostic relevance for S1P lyase expression was observed. Collectively, the results suggest that the immunohistochemical detection of SphK1 may be a promising predictive marker in NSCLC patients treated with adjuvant platinum‑based chemotherapy.

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