CESC is a general tumor in women. With the upgrowth of standard treatment options for CESC patients with concurrent chemotherapy and brachytherapy, it has improved of the five-year survival rate, while the prognosis is poor 28. nevertheless, there is a pressing need for promising prognostic biomarkers to assess pressing patients risk with metastatic CESC and corresponding effective therapeutic targets that can improve clinical outcomes.
More and more evidence shows that S1P is associated with angiogenesis, cell proliferation, chemotaxis, migration and differentiation, and is also associated with the cancer biology. These S1PRs seems to be specific of tissues, has been shown to be consist of the cell proliferation regular pattern, surviving in various cancer types. S1PR2 roles in cancer remains agonistical. According to reports, S1PR2 can act as an anti-cancer and cancer-promoting receiver. For example, in B-cell lymphoma, glioblastoma, and melanoma, S1PR2 plays an anti-cancer receiver. On the other hand, it is reported that in prostate cancer, S1PR2 plays a carcinogenic receiver. A review introduced that on the roles of S1PR2 in cancers referred to the affect of this receiver on developing of tumor and headway is the specific of cell-type, because of its taking part with the specific G proteins to regulate physiological functions 29. Therefore, despite the existence of context-specific and controversial evidence, the knowledge of S1PR2 in CESC is still insufficient and further research is needed. In this study, we first performed a pan-cancer analyzed of S1PR2 expression used Cancer Genome Atlas (TCGA) data, and used it to verify the S1PR2 expression. Survival analysis of S1PR2 in these cancer types of interest indicated that patients of CESC with low S1PR2 expression have a poorer prognosis. And we further found down-regulated S1PR2 expression is positively correlated with patients with high clinical stages, more histological types of squamous cell carcinoma, and poor primary treatment outcomes. ROC curve analysis indicates S1PR2 might be a promising diagnostic biomarker in distinguishing CESC from normal tissues. S1PR2 might be a promising biomarker for impoverished prognosis of CESC.
S1PR2 participates in differentiation, cell proliferation, angiogenesis, migration and chemotaxis through the sphingolipid signaling pathway. TP inhibits the SPHK-S1P signaling pathway and effectively reduces the levels of S1P and the expression of SPHK1/S1PR1/S1PR2, and markedly suppressing the S1P-mediated phosphorylation activation of ERK protein in macrophages 30. Our co-expression analysis indicated that the expression of S1PR2 was markedly related to the expression of RHOA, GNA11, GNA12, GNAI1, GNAI2, and GNAQ. We speculate that the down-regulation of S1PR2 will effect the entire pathway, and it possibility could be examined in future findings.
Numerous studies have convinced that the tumor immune cell infiltration could effect the usefulness of immunotherapy, radiotherapy or chemotherapy and the prognostication of cancer patients 31–33. This work shows that S1PR2 is markedly positively related to various immune cells, involving dendritic cells, macrophages, CD4 + T cells, neutrophils, and B cells in CESC. In addition, S1PR2 is also significantly positively correlated with these biomarkers of infiltrating immune cells. These results indicate tumor immune infiltration may not wholly explain the carcinogenic effects of S1PR2 mediated in HCC.
The usefulness of immunotherapy requires sufficient immune cells to infiltrate the tumor microenvironment, and relies on the full expression of immune checkpoints 34. Therefore, this study more evaluated the related about S1PR2 with immune checkpoints. The findings indicate that S1PR2 is closely related to CTLA-4 or PD1 in CESC, showing that aiming S1PR2 may enhance the efficacious of immunotreatment in CESC.
In conclusion, this study clarified that S1PR2 is under-expressed in many human cancers (involving CESC) and is positively related to the poor prognosis of CESC. Furthermore, our current research results also indicate that S1PR2 may exert its anti-cancer effect by increasing the tumor immune cell infiltration and the expression of immune checkpoint. Therefore, these findings could be verified more through large-scale clinical trials and basic experiments in the future.