// Jinhong Wang 1 , Dong Kang 2 , Yu Yao 3 , Anna Shen 4 , Deguang Yang 4 and Tao Zhou 4 1 Department of respiration, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China 2 Hui qiao Department, South Hospital of Southern Medical University, Guangzhou, Guangdong, China 3 Department of Anesthesiology, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China 4 Department of Cardiovascular, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China Correspondence to: Tao Zhou, email: zhoutao6240@sina.com Keywords : suppressor of cytokine signaling 3; non-small cell lung cancer; promoter methylation; treatment response; prognosis Received: April 07, 2017 Accepted: July 26, 2017 Epub: December 11, 2017 Abstract We aimed to test if suppressor of cytokine signaling 3 (SOCS3) expression and its gene promoter methylation status are predictors for the treatment response to Platinum-based chemotherapy, which is a key factor affecting the prognosis of advanced Non-small cell lung cancer (NSCLC). Methods We enrolled patients with inoperable advanced stage of NSCLC. All patients received Platinum-based chemotherapy and response evaluation and prognosis analyses were performed. Meanwhile, the immunohistochemical analysis for tumor SOCS3 expression and methylation analysis of SOCS3 promoter methylation by PCR were conducted. In vitro, two lung cancer cell Lines and si-RNA transfection against SOCS3 followed by viability and apoptosis assay. Results We found that patients with high SOCS3 tend to have low tumor stage and high tumor differentiation status and a higher rate of good response to chemotherapy. SOCS3 methylation status is also closely related to chemotherapy response. Prognosis analyses, however, revealed that only the SOCS3 expression, instead of its promoter methylation status, predicts the prognosis of NSCLC receiving chemotherapy. Our in vitro data show that the proapoptotic effect of SOCS3 on lung cancer is mediated by JAK2/STAT3. Conclusion Considering the lack of reliable biomarker to predict patient’ therapeutic response to chemotherapy, our finding may be helpful for clinic evaluation of patients undergoing chemotherapy.