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Background: Esophageal squamous cell carcinoma(ESCC) is one of the most common tumors worldwide. Esophagectomy with three-field lymph node dissection(3FLND) is the radical surgical procedure for esophageal cancer. However, 3FLND is not widely used due to it's higher mortality rate and higher incidence of postoperative complications. There is an urgent need to identify novel biomarkers that can guide the most proper lymph-node dissection in esophageal cancer patients.Method: Ninety-two patients with thoracic ESCC undergoing 3FLND were enrolled into our study from the Department of Thoracic Surgery of the Fourth Hospital affiliated to the Hebei Medical University and Hebei General Hospital between Jun 2011 and Dec 2015. Retrospectively collected data from these 92 patients was used to explore the relationship between the lymph-node metastasis、recurrence and the SPRY4-IT1 expression level and to determine whether 3FLND should be performed in patients with thoracic ESCC.Results: The findings revealed that the SPRY4-IT1 expression was significantly higher in esophageal cancer tissues than in adjacent noncancerous tissues. (P < 0.01). Furthermore, the high expression of SPRY4-IT1 was significantly correlated with tumor differentiation (P = 0.029), T classification (P = 0.013), lymph node metastasis(P = 0.022) and pathological stage (P = 0.001). The increased expression of SPRY4-IT1 was associated with a higher risk of cervical and superior mediastinal lymph-node metastasis(P = 0.039).However, no significant association was observed between the risk of cervical and superior mediastinal lymph-node recurrence and the SPRY4-IT1 expression level in the thoracic ESCC patients performed 3FLND(P = 0.509).Conclusions: Our data support the assumption that the high expression of SPRY4-IT1 is associated with a high risk of lymph node metastasis and it has potential application as a indicator for guiding on three-field lymph node dissection in patients with thoracic ESCC. Randomized controlled trials with a large cohort of patients will be needed to confirm this conclusion in the future. [ABSTRACT FROM AUTHOR]