Prognostic Impact of Sphingosine Kinase 1 in Nonsmall Cell Lung Cancer

Abstract

Bioactive sphingolipid is clearly relevant to lung physiology. The relationship of the bioactive sphingolipid pathway to pulmonary disease has been studied in cellular, tissue, and animal model, including lung cancer models. The samples of 53 patients diagnosed with nonsmall cell lung carcinoma (NSCLC) between June 2009 and May 2014 at our hospital were analyzed. Immunohistochemical (IHC) analysis was performed. The degree of immunostaining was reviewed and scored. Using this method of assessment, we evaluated the IHC score of sphingosine kinase 1 (SPHK1), vimentin, E-cadherin, and Ki-67. Both invasive adenocarcinoma cell and squamous cell carcinoma cell were well stained by SPHK1, and fibroblasts were also well stained by SPHK1. Although the IHC score of SPHK1 was not significantly differed between invasive adenocarcinoma and squamous cell carcinoma, the IHC scores of fibroblast, vimentin, and Ki-67 were higher in squamous cell carcinoma than invasive adenocarcinoma. Correlation among IHC scores in each of invasive adenocarcinoma and squamous cell carcinoma was performed. SPHK1 had positive correlation with both fibroblast and Ki-67, and fibroblast and Ki-67 had also positive correlation in invasive adenocarcinoma. On the contrary, SPHK1 had no significant correlation with fibroblast, and had negative correlation with Ki-67 in squamous cell carcinoma. Although there was not significant prognostic difference in SPHK1 score ( P = .09), IHC score high group tended to be worse on relapse-free survival. SPHK1 might be prognostic factor in lung-invasive adenocarcinoma and novel target for drug against lung-invasive adenocarcinoma.

Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models

“…In addition, Fingolimod has also been demonstrated to affect sphingosine-1-kinases activity through phosphorylation inhibition or degradation [ 28 ]. Interestingly, sphingosine-1-kinase 1 is highly expressed with a more advanced disease stage in NSCLC tissues and its high expression level is correlated with poor NSCLC patient prognosis [ 73 , 74 ]. Thus, an alternative mechanism of action independent of S1PRs inhibition might be due to sphingosine-1-kinase 1 modulation and consequent tumor progression in NSCLC cancer.…”

E-cadherin expression in the tumor microenvironment of advanced epidermal growth factor receptor-mutant lung adenocarcinoma and the association with prognosis

“…In the case of E-cadherin and vimentin, the staining intensity was graded as per the membranous expression: 0 equals to no expression; 1 equals to fragmented membranous and/or weak to moderate expression; 2 equals to fragmented strong or fully membranous moderate expression; and 3 equals to fully membranous strong expression. The percentage of immunoreactive positive tumor cells was graded as: 0 (no positive tumor cells), 1 (less than 10% positive tumor cells), 2 (10–50% positive tumor cells), and 3 (more than 50% positive tumor cells) [ 20 ]. An expression score was defined as the product of the percentage of immunoreactive positive tumor cells graded and the staining intensity.…”