Serum sphingosine-1-phosphate receptor 3 serves as a biomarker for identifying PDAC

Sphingosine-1-phosphate receptor 3 (S1PR3), a receptor of sphingosine-1-phosphate (S1P), participates in cancer progression. However, no study has investigated the S1PR3 expression in pancreatic ductal adenocarcinoma (PDAC).

The S1PR3 expression in patients with PDAC and its role in predicting PDAC were investigated.

We investigated the tissue and serum levels of S1PR3 in patients with PDAC by using immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Silencing RNA (siRNA) was used to inhibit the expression of S1PR3 in the PDAC cell line, after which the invasion ability of the cells and the release of inflammatory factors from the cells were evaluated by a Transwell assay and flow cytometry analysis, respectively.

Decreased S1PR3 expression in human PDAC tissues was significantly correlated with distant metastasis. Similarly, the ELISA results revealed that the serum S1PR3 concentrations in patients with PDAC (3.94 ± 0.47 ng/ml) were clearly lower than those in the controls (8.40 ± 0.63 ng/ml) (P < 0.001). In addition, serum S1PR3 levels clearly predict PDAC. The area under the receiver operating characteristic curve (AUC) for S1PR3 was 0.79, with 74.24% sensitivity and 71.29% specificity. The area under the curve (AUC) for the combination of carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA199) for S1PR3 was 0.97, with 91.43% sensitivity and 89.66% specificity, which was better than those of either the alone or pairwise combinations. Notably, cell experiments revealed that silencing S1PR3 promoted PDAC cell invasion and increased the levels of interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-17A (IL-17A) and interferon gamma (IFN-γ) in the cell culture medium.

Our results demonstrated that the downregulation or loss of S1PR3 expression might be used for the diagnosis of PDAC and is closely associated with the malignant progression of PDAC.