The prognostic role of sphingosine kinase-1 and S1P lyase protein expression in patients with non- small cell lung cancer

Background: Sphingosine 1-phosphate (S1P) has emerged as a key lipid mediator that promotes tumor cell proliferation, survival, migration and angiogenesis. Sphingosine kinase-1 (SphK1) and S1P lyase are the main enzymes that control synthesis and degradation of S1P.Herein we report for the first time the prognostic and predictive value of both SphK1 and S1P lyase expression in patients with non-small cell lung cancer (NSCLC) treated with adjuvant platinum-based chemotherapy.

Material and methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from 120 NSCLC patients were stained immunohistochemically using antibodies against SphK1 and S1P lyase, and the results correlated with all available clinicopathological factors.

Results: Cross-tabulation of SphK1 expression and survival showed that the risk of relapse is higher in patients with increased SphK1 expre­ssion (histoscore ≥ 75), irrespective of the stage (Odds ratio = 3,333, overall accuracy = 68,8 %, p = 0,01). Univariate Cox regression model of survi­val also showed the increase of the risk of relapse in patients with SphK1 ≥ 75 expression (p = 0,006, HR = 1.004, 95 % CI [1,001; 1,006]). Multivariate sur­vival analysis, using the Cox regression method showed that SphK1 represents an additional risk factor for NSCLC relapse, together with disease grade, stage, tumor size (T) and nodal status (N) (p = 0,038, HR = 2,048 95 % CI [1,039; 4,037]). Increased cytoplasmic expression of S1P lyase was significantly related to the increased risk ofNSCLC progression in patients with stage III-IV NSCLC (p = 0,022).

Conclusion: Collectively, our data suggest that the immunohistochemical detection of sphingolipid metabolism pathway enzymes, particularly SphK1 and S1P lyase might represent promising prognostic markers in NSCLC patients treated with adjuvant platinum-based chemotherapy.