Aberrant expression of sphingosine-1-phosphate receptor 1 correlates with metachronous liver metastasis and poor prognosis in colorectal cancer.

There are currently no accurate predictive markers of metachronous liver metastasis from colorectal cancer. Recent studies demonstrated that the expression patterns of sphingosine-1-phosphate receptor 1 (S1PR1) are altered in several tumors, but in colorectal cancer, the patterns remain unknown. Our study was designed to evaluate the expression and prognostic significance of S1PR1 protein in patients with colorectal cancer. The expression of S1PR1 was detected using the tissue microarray technique and immunohistochemical method and compared with clinicopathological parameters in 153 colorectal cancer patients. The prognostic value of S1PR1 expression was evaluated by Kaplan-Meier and Cox regression analysis. A molecular prognostic stratification scheme incorporating S1PR1 expression was determined by using receiver operating characteristic (ROC) analysis. S1PR1 was significantly highly expressed in 70.6 % (108/153) of the colorectal cancer lesions compared to their high expressions in only 5.9 % (9/153) of the adjacent non-cancerous tissues. Upregulated expression of S1PR1 was significantly associated with depth invasion and metachronous liver metastasis. Increased S1PR1 expression in colorectal cancer was positively correlated with poor overall survival. Multivariate survival analysis suggested that S1PR1 expression was an independent prognostic indicator for the disease. Applying the prognostic value of S1PR1 density to TNM stage system showed a better prognostic value in patients with colorectal cancer. Aberrant S1PR1 expression in colorectal cancer was associated with metachronous liver metastasis and worse survival outcome, and also, it was an independent prognostic factor. According to our analysis, combined TNM stage and intratumoral expression of S1PR1 demonstrated a better prognostic value than any of these two parameters alone. Conclusively, we suggest that detection and analysis of S1PR1 expression in colorectal cancer tissue might be used for predicting prognosis of colorectal cancer.