LAUSR

Background: Expression of cytokines and growth factors have been shown to be highly correlated with the prognosis in esophageal squamous cell carcinoma (ESCC), a dead disease with poor prognosis. The suppressor of cytokine signaling (SOCS) family of proteins are key factors in the feedback system that regulates the expression of cytokines and growth factors in cells. Yet the role of the SOCS family of proteins in ESCC is hardly known.Method:We analyzed the prognostic effects of 16 single nucleotide polymorphisms (SNPs) within the SOCS family of genes in 632 ESCC patients using MassARRAY system. The underlying mechanisms of SOCS SNPs effect on prognosis was analyzed using luciferase assay. The possible functions of SOCS5 in ESCC cells were analyzed by transiently over-expression. Result: We repeatedly observed that the 3 SNPs in SOCS5, SOCS5:rs3814039, SOCS5:rs3738890, and SOCS5: rs3768720, were significantly correlated with both overall (OS) and progression-free survival (PFS) of ESCC patients (rs3814039, p1⁄40.032 for OS and p1⁄40.009 for PFS; rs3738890, p1⁄40.016 for OS, and p1⁄40.008 for PFS; rs3768720, p1⁄40.005 for OS and p1⁄40.002 for PFS). SOCS5: rs3768720 was also significantly associated with distant metastasis (Ptrend1⁄40.028). The luciferase assay revealed that SOCS5:rs3814039 and SOCS5: rs3738890 might influence the prognosis by regulating SOCS5 expression. Functional analysis demonstrated SOCS5 was able to regulate epidermal growth factor receptor (EGFR) expression and migration activity of ESCC cells. Conclusion: Our study demonstrates the roles of SOCS5 in ESCC prognosis. The genetic polymorphisms of SOCS5 could serve as a novel therapeutic biomarker for improving the prognosis of ESCC.