The immunohistochemical expression of sphingosine kinase 1 and S1P lyase in non-small cell lung cancer: a tissue microarray study

Abstract

Background Bioactive sphingolipid sphingosine-1-phosphate (S1P) plays an important role in various aspects of cancer biology, including cell proliferation, transformation, survival and migration. Sphingosine kinase 1 (SphK1) is a key enzyme, responsible for S1P production from sphingosine. On the other hand, S1P is irreversibly degraded by the sphingosine-1-phosphate lyase (SPL). We aimed to investigate the possible importance of the immunohistochemical expression of Sphk1 and S1P lyase in patients with NSCLC. Methods Tumor tissue microarrays (TMA) were constructed from 201 paraffin blocks consisted of representable parts of primary lung cancer. TMA blocks were cut at 4 μm sections and stained for antibodies against Sphk1 and SPL, according to standard immunohistochemical (IHC) protocol. IHC stained slides were evaluated by two independent investigators using histoscore method. Correlations between the levels of both examined proteins and all available clinicopathological features were analyzed using SPSS statistical software. Results Cox-regression analysis showed that in patients with stage III-IV NSCLC, without neo-adjuvant chemotherapy, the expression of SphK1 positively correlates with better disease free survival (DFS); increased SphK1 expression is associated with decreased risk of relapse ( p = 0.020, HR = 0.383). The same analysis also showed that the risk of NSCLC relapse is significantly higher in stage III–IV patients positive for SPL ( p = 0.0003, HR = 1.005), while there is no difference in the SPL negative group. Conclusion According to our study results immunohistochemical expression of Sphk1 and SPL might serve as additional useful prognostic markers for patients with advanced non-small-cell lung cancer; however, more extended study is necessary.