J Cancer 2021; 12(8):2216-2229. doi:10.7150/jca.51806

Research Paper

The genetic effect and molecular function of the SOCS5 in the prognosis of esophageal squamous cell carcinoma

Pei-Wen Yang1, Ya-Han Chang1, Li-Fan Wong1, Ching-Ching Lin1, Pei-Ming Huang1, Min-Shu Hsieh2, Jang-Ming Lee1✉

1. Department of Surgery, National Taiwan University Hospital & National Taiwan University College of Medicine.
2. Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.

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Citation:
Yang PW, Chang YH, Wong LF, Lin CC, Huang PM, Hsieh MS, Lee JM. The genetic effect and molecular function of the SOCS5 in the prognosis of esophageal squamous cell carcinoma. J Cancer 2021; 12(8):2216-2229. doi:10.7150/jca.51806. Available from https://www.jcancer.org/v12p2216.htm

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Abstract

Expression of cytokines and growth factors have been shown to be highly correlated with the prognosis of esophageal squamous cell carcinoma (ESCC), a deadly disease with poor prognosis. The suppressor of cytokine signaling (SOCS) family of proteins are key factors in regulating cytokines and growth factors. Yet the role of the SOCS proteins in ESCC is hardly investigated. We currently investigated the prognostic role of SOCS5 in ESCC. We analyzed the prognostic effects of 16 single nucleotide polymorphisms (SNPs) within the SOCS genes in 632 ESCC patients. 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, p=0.032 for OS and p=0.009 for PFS; rs3738890, p=0.016 for OS, and p=0.008 for PFS; rs3768720, p=0.005 for OS and p=0.002 for PFS). SOCS5: rs3768720 was also significantly associated with distant metastasis (Ptrend=0.028).

The luciferase assay revealed that SOCS5:rs3814039 and SOCS5: rs3768720 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. Furthermore, Patients with strong SOCS5 in normal tissues exhibited significantly better PFS (P=0.049) and reduced risk of distant metastasis (P=0.004) compared to those with weak SOCS5 expression. Overall, our study demonstrates the novel function of SOCS5 in ESCC prognosis. The genetic polymorphisms and expression of SOCS5 could serve as a novel therapeutic biomarker for improving the prognosis of ESCC.

Keywords: esophageal cancer, esophageal squamous cell carcinoma (ESCC), suppressor of cytokine signaling-5 (SOCS5), single nucleotide polymorphisms (SNPs), epidermal growth factor receptor (EGFR)